Lee HJ

References (55)

Title : Anti-Cancer Effect of Neural Stem Cells Transfected with Carboxylesterase and sTRAIL Genes in Animals with Brain Lesions of Lung Cancer - Kim_2023_Pharmaceuticals.(Basel)_16_
Author(s) : Kim JH , Ahn JS , Lee DS , Hong SH , Lee HJ
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.
ESTHER : Kim_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : Kim_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 37631070

Title : Effects of sugammadex versus neostigmine on postoperative nausea and vomiting after general anesthesia in adult patients:a single-center retrospective study - Ju_2023_Sci.Rep_13_5422
Author(s) : Ju JW , Hwang IE , Cho HY , Yang SM , Kim WH , Lee HJ
Ref : Sci Rep , 13 :5422 , 2023
Abstract : We aimed to compare the effect of sugammadex to that of neostigmine with respect to the occurrence of postoperative nausea and vomiting (PONV) during the first 24 h following general anesthesia. This retrospective cohort study included patients who underwent elective surgery under general anesthesia in 2020 at an academic medical center in Seoul, South Korea. The exposure groups were determined according to whether the patient received sugammadex or neostigmine as a reversal agent. The primary outcome was PONV occurrence during the first 24 h postoperatively (overall). The association between the type of reversal agent and primary outcome was investigated using logistic regression while adjusting for confounding variables using stabilized inverse probability of treatment weighting (sIPTW). Of the 10,912 patients included in this study, 5,918 (54.2%) received sugammadex. Sugammadex was associated with a significantly lower incidence of overall PONV (15.8% vs. 17.7%; odds ratio, 0.87; 95% confidence interval [CI], 0.79-0.97; P = 0.010) after sIPTW. In conclusion, compared with neostigmine/glycopyrrolate, sugammadex use has a lower risk of PONV during the first 24 h following general anesthesia.
ESTHER : Ju_2023_Sci.Rep_13_5422
PubMedSearch : Ju_2023_Sci.Rep_13_5422
PubMedID: 37012336

Title : Honeysuckle Berry (Lonicera caerulea L.) Inhibits Lipase Activity and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice - Kim_2022_Molecules_27_
Author(s) : Kim JY , Lee YS , Park EJ , Lee HJ
Ref : Molecules , 27 : , 2022
Abstract : Honeysuckle berry (HB, Lonicera caerulea L.) is an oriental herbal medicine reported to have beneficial effects on metabolic disorders, such as obesity and non-alcoholic fatty liver disease. The fruit part of HB is rich in anthocyanin, a type of polyphenol. Most studies credit the antioxidant and anti-inflammatory properties of HB as the mechanisms of its effectiveness. This study investigated the inhibitory effects of HB on lipase using an in vitro assay and the modulatory effect of HB on gut microbiota in high-fat diet (HFD)-fed mice. HB inhibited pancreatic lipase activity with IC(50) values of approximately 0.47 mg/mL. The fecal triglyceride (TG) levels were higher from the HFD of the HB-fed mice than they were for the control mice. Moreover, the fecal microbiota from the HFD of the HB-fed mice had relatively lower Firmicutes and higher Bacteroidetes than that from the HFD-only mice. These results suggest that HB modulates gut microbiota composition, which may contribute to body fat reduction. Hence, HB could present a useful agent for treating metabolic diseases through lower TG uptake and the regulation of gut microflora.
ESTHER : Kim_2022_Molecules_27_
PubMedSearch : Kim_2022_Molecules_27_
PubMedID: 35897908

Title : Antifungal and carboxylesterase-producing bacteria applied into corn silage still affected the fermented total mixed ration - Paradhipta_2022_Anim.Biosci__
Author(s) : Paradhipta DHV , Seo MJ , Jeong SM , Joo YH , Lee SS , Seong PN , Lee HJ , Kim SC
Ref : Anim Biosci , : , 2022
Abstract : OBJECTIVE: This study investigated the effects of corn silage as a source of microbial inoculant containing antifungal and carboxylesterase-producing bacteria on fermentation, aerobic stability, and nutrient digestibility of fermented total mixed ration (FTMR) with different energy levels. METHODS: Corn silage was used as a bacterial source by ensiling for 72 d with an inoculant mixture of Lactobacillus brevis 5M2 and L. buchneri 6M1 at a 1:1 ratio. The corn silage without or with inoculant (CON vs. MIX) was mixed with the other ingredients to formulate for low and high energy diets (LOW vs. HIGH) for Hanwoo steers. All diets were ensiled into 20 L mini silo (5 kg) for 40 d in quadruplicate. RESULTS: The MIX diets had lower (p<0.05) acid detergent fiber with higher (p<0.05) in vitro digestibilities of dry matter and neutral detergent fiber compared to the CON diets. In terms of fermentation characteristics, the MIX diets had higher (p<0.05) acetate than the CON diets. The MIX diets had extended (p<0.05) lactic acid bacteria growth at 4 to 7 d of aerobic exposure and showed lower (p<0.05) yeast growth at 7 d of aerobic exposure than the CON diets. In terms of rumen fermentation, the MIX diets had higher (p<0.05) total fermentable fraction and total volatile fatty acid, with lower (p<0.05) pH than those of CON diets. The interaction (p=0.036) between inoculant and diet level was only found in the immediately fermentable fraction, which inoculant was only effective on LOW diets. CONCLUSION: Application of corn silage with inoculant on FTMR presented an antifungal effect by inhibiting yeast at aerobic exposure and a carboxylesterase effect by improving nutrient digestibility. It also indicated that fermented feedstuffs could be used as microbial source for FTMR. Generally, the interaction between inoculant and diet level had less effect on this FTMR study.
ESTHER : Paradhipta_2022_Anim.Biosci__
PubMedSearch : Paradhipta_2022_Anim.Biosci__
PubMedID: 36397704

Title : Prenatal glucocorticoid exposure selectively impairs neuroligin 1-dependent neurogenesis by suppressing astrocytic FGF2-neuronal FGFR1 axis - Choi_2022_Cell.Mol.Life.Sci_79_294
Author(s) : Choi GE , Chae CW , Park MR , Yoon JH , Jung YH , Lee HJ , Han HJ
Ref : Cell Mol Life Sciences , 79 :294 , 2022
Abstract : Exposure to maternal stress irreversibly impairs neurogenesis of offspring by inducing life-long effects on interaction between neurons and glia under raging differentiation process, culminating in cognitive and neuropsychiatric abnormalities in adulthood. We identified that prenatal exposure to stress-responsive hormone glucocorticoid impaired neurogenesis and induced abnormal behaviors in ICR mice. Then, we used human induced pluripotent stem cell (iPSC)-derived neural stem cell (NSC) to investigate how neurogenesis deficits occur. Following glucocorticoid treatment, NSC-derived astrocytes were found to be A1-like neurotoxic astrocytes. Moreover, cortisol-treated astrocytic conditioned media (ACM) then specifically downregulated AMPA receptor-mediated glutamatergic synaptic formation and transmission in differentiating neurons, by inhibiting localization of ionotropic glutamate receptor (GluR)1/2 into synapses. We then revealed that downregulated astrocytic fibroblast growth factor 2 (FGF2) and nuclear fibroblast growth factor receptor 1 (FGFR1) of neurons are key pathogenic factors for reducing glutamatergic synaptogenesis. We further confirmed that cortisol-treated ACM specifically decreased the binding of neuronal FGFR1 to the synaptogenic NLGN1 promoter, but this was reversed by FGFR1 restoration. Upregulation of neuroligin 1, which is important in scaffolding GluR1/2 into the postsynaptic compartment, eventually normalized glutamatergic synaptogenesis and subsequent neurogenesis. Moreover, pretreatment of FGF2 elevated neuroligin 1 expression and trafficking of GluR1/2 into the postsynaptic compartment of mice exposed to prenatal corticosterone, improving spatial memory and depression/anxiety-like behaviors. In conclusion, we identified neuroligin 1 restoration by astrocytic FGF2 and its downstream neuronal nuclear FGFR1 as a critical target for preventing prenatal stress-induced dysfunction in glutamatergic synaptogenesis, which recovered both neurogenesis and hippocampal-related behaviors.
ESTHER : Choi_2022_Cell.Mol.Life.Sci_79_294
PubMedSearch : Choi_2022_Cell.Mol.Life.Sci_79_294
PubMedID: 35562616

Title : The Oil Formulation Derived from Moringa Oleifera Seeds Ameliorates Behavioral Abnormalities in Water-immersion Restraint Stress Mouse Model - Purwoningsih_2022_J.Exp.Pharmacol_14_395
Author(s) : Purwoningsih E , Arozal W , Lee HJ , Barinda AJ , Sani Y , Munim A
Ref : J Exp Pharmacol , 14 :395 , 2022
Abstract : PURPOSE: Repeated stress events are well known to be associated with the onset of behavioral abnormalities including depression, anxiety and memory impairment. In spite of the traditional uses of Moringa oleifera (MO), no experimental evidence for its use against chronic stress exists. Here, we investigated whether seed oil from MO (MOO) could improve behavior abnormalities of chronic stress mice induced by water-immersion restraint stress (WIRS) and the underlying mechanism. METHODS: BALB/C male mice at 12 weeks of age were exposed to chronic WIRS for two weeks and divided in to four groups: normal group, WIRS group, WIRS+MOO1 group (treated with MOO at the dose of 1 mL/kg BW), and WIRS+MOO2 group (treated with MOO 2 mL/kg BW). The MOO treatment was given orally for 23 days. On day 24, we checked the behavior parameters, the plasma level of cortisol, acetylcholinesterase (AChE) activity in hippocampus, mRNA expression level of brain-derived neurotrophic factor (BDNF) and oxidative stress parameters in brain tissues. In addition, we also checked the histopathological features of the gastric mucosa wall. RESULTS: Administration of MOO ameliorated anxiety-like, depression-like and memory impairment phenotypes in the WIRS mouse model although the plasma cortisol concentrations were comparable among the groups. Of note, MOO both in two doses could suppress the AChE activity in hippocampus tissue and ameliorated the MDA level in prefrontal cortex tissue in mice exposed to WIRS. Although only WIRS+MOO2 group could increase the mRNA expression of BDNF, the histopathological gastric mucosa wall features were improved in all MOO groups. CONCLUSION: Taken together, these finding suggested that MOO may have a neuroprotective effect in the mouse model of WIRS as evidenced by improving the abnormal behaviors through enhancing mRNA expression level of BDNF, inhibited AChE activity, and prevented the increase of MDA level in the brain.
ESTHER : Purwoningsih_2022_J.Exp.Pharmacol_14_395
PubMedSearch : Purwoningsih_2022_J.Exp.Pharmacol_14_395
PubMedID: 36583146

Title : Donepezil Regulates LPS and Abeta-Stimulated Neuroinflammation through MAPK\/NLRP3 Inflammasome\/STAT3 Signaling - Kim_2021_Int.J.Mol.Sci_22_
Author(s) : Kim J , Lee HJ , Park SK , Park JH , Jeong HR , Lee S , Lee H , Seol E , Hoe HS
Ref : Int J Mol Sci , 22 : , 2021
Abstract : The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Abeta-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 microM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 microM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Abeta-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Abeta-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
ESTHER : Kim_2021_Int.J.Mol.Sci_22_
PubMedSearch : Kim_2021_Int.J.Mol.Sci_22_
PubMedID: 34638977

Title : Post-market utilization patterns of Alzheimer's disease treatments in South Korea: comparison with countries with universal health coverage - Lee_2021_Eur.J.Clin.Pharmacol__
Author(s) : Lee HJ , Roughead EE , Han E , Lee J , Kalisch Ellett L
Ref : European Journal of Clinical Pharmacology , : , 2021
Abstract : PURPOSE: This study aimed to compare the utilization of Alzheimer's disease (AD) treatments, donepezil, galantamine, rivastigmine, and memantine, in Korea with Australia and other countries with universal health coverage. METHODS: Reimbursement criteria and the patent status of four AD treatments in Korea and Australia were reviewed. The monthly spending and utilization of the treatments were extracted from the national electronic database in Korea and Australia. The defined daily dose per 1000 elderly population per day (DDD/1000e/day) were calculated from July 2008 to June 2019. Annual cost trends of Norway and England were compared with Korea and Australia. RESULTS: With the highest share of the use of donepezil in both countries, the cost and utilization of AD treatments in Korea increased more rapidly and remained higher than Australia. The cost of AD treatments in Korea increased by 15.5% every year during the study period, while the spending of the same drugs in Australia decreased by 10.5% annually. The utilization in DDD/1000e/day of AD treatments in Korea increased by 18.3% annually compared with 1.4% in Australia. When compared with Norway and England, countries with similar universal health coverage (UHC) system and elderly polupation, the cost of AD treatments in Korea was still higher with the opposite trend from other countries. CONCLUSIONS: Despite the similar UHC systems, there were considerable differences in the post-market utilization of AD treatments in Korea from Australia and other countries. This results can be attributed to differences in re-assessment system, pricing and reimbursement policies, and prescribing culture. This study provides a baseline to explore more comprehensive cross-country studies on rational use of medicines.
ESTHER : Lee_2021_Eur.J.Clin.Pharmacol__
PubMedSearch : Lee_2021_Eur.J.Clin.Pharmacol__
PubMedID: 33409682

Title : Effects of Inoculants Producing Antifungal and Carboxylesterase Activities on Corn Silage and Its Shelf Life against Mold Contamination at Feed-Out Phase - Paradhipta_2021_Microorganisms_9_
Author(s) : Paradhipta DHV , Joo YH , Lee HJ , Lee SS , Noh HT , Choi JS , Kim J , Min HG , Kim SC
Ref : Microorganisms , 9 : , 2021
Abstract : The present study aimed to investigate effects of dual-purpose inoculants (antifungal and carboxylesterase activities) not only on corn silage quality, but also its shelf life against mold contamination at feed-out phase. Corn forage was ensiled for 252 d with different inoculants of the following: control (CON), Lactobacillus brevis 5M2 (5M), Lactobacillus buchneri 6M1 (6M), and mixture of 5M and 6M at 1:1 ratio (MIX). After ensiling, corn silage was contaminated with Fusarium graminearum. Silages applied inoculants had positive effects by increased organic acid and lactic acid bacteria, and decreased undesirable microbes. At feed-out phase, contamination of F. graminearum into corn silage had a negative effect on aerobic stability caused by increased growth of undesirable microbes. However, silages applied inoculants had positive effects by decreased undesirable microbes and extended lactic acid bacteria and aerobic stability. Generally, MIX silage presented better effects on organic acid production, rumen degradation, inhibition of undesirable microbes, and aerobic stability than 5M silage and 6M silage. The present study concluded that application of inoculants into corn silage had positive effects on fermentation characteristics and extended shelf life against mold contamination at feed-out phase. A mixed inoculant appeared to have better effects of antifungal and carboxylesterase than a single inoculant.
ESTHER : Paradhipta_2021_Microorganisms_9_
PubMedSearch : Paradhipta_2021_Microorganisms_9_
PubMedID: 33800497

Title : Application of lactic acid bacteria producing antifungal substance and carboxylesterase on whole crop rice silage with different dry matter - Lee_2021_Anim.Biosci_34_1029
Author(s) : Lee SS , Paradhipta DHV , Lee HJ , Joo YH , Noh HT , Choi JS , Ji KB , Kim SC
Ref : Anim Biosci , 34 :1029 , 2021
Abstract : OBJECTIVE: This study was conducted to investigate effects of antifungal substance and carboxylesterase-producing inoculant on fermentation indices and rumen degradation kinetics of whole crop rice (WCR) silage ensiled at different dry matter (DM) contents. METHODS: Dual-purpose inoculants, Lactobacillus brevis 5M2 and Lactobacillus buchneri 6M1, confirmed both activities of antifungal and carboxylesterase in the previous study. The WCR at mature stage was chopped, and then wilted to obtain three different DM contents consisting of 35.4%, 43.6%, and 51.5%. All WCR forages were applied distilled water (CON) or mixed inoculants with 1:1 ratio at 1x105 colony forming unit/g (INO), and ensiled into 20 L mini silo (5 kg) in quadruplicates for 108 d. RESULTS: The INO silages had lower lactate (p<0.001) and butyrate (p = 0.022) with higher acetate (p<0.001) and propionate (p<0.001) than those of CON silages. Ammonia-N (p<0.001), lactate (tendency; p = 0.068), acetate (p = 0.030), and butyrate (p<0.001) concentrations of INO silages decreased linearly with increasing DM content of WCR forage. The INO silages presented higher lactic acid bacteria (p<0.001) with lower molds (p< 0.001) than those of CON silages. Yeasts (p = 0.042) and molds (p = 0.046) of WCR silages decreased linearly with increasing DM content of WCR forage. In the rumen, INO silages had higher the total degradable fraction (p<0.001), total volatile fatty acid (tendency; p = 0.097), and acetate (p = 0.007), but lower the fractional degradation rate (p = 0.011) and propionate (p<0.001) than those of CON silage. The total degradable fraction (p<0.001), total volatile fatty acid (p = 0.001), iso-butyrate (p = 0.036), and valerate (p = 0.008) decreased linearly with increasing DM content of WCR forage, while the lag phase (p<0.001) was increased linearly. CONCLUSION: This study concluded that application of dual-purpose inoculants on WCR silage confirmed antifungal and carboxylesterase activities by inhibiting mold and improving rumen digestibility, while increase of wilting times decreased organic acids production and rumen digestibility.
ESTHER : Lee_2021_Anim.Biosci_34_1029
PubMedSearch : Lee_2021_Anim.Biosci_34_1029
PubMedID: 33152212

Title : Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice - Kim_2021_Molecules_26_
Author(s) : Kim CJ , Ryu HY , Lee S , Lee HJ , Chun YS , Kim JK , Yu CY , Ghimire BK , Lee JG
Ref : Molecules , 26 : , 2021
Abstract : Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-beta) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In invitro tests, HLJG0701-beta inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In invivo tests, after HLJG0701-beta was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-beta produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-beta was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both invitro and invivo tests confirmed that HJG0701-beta administration can lead to memory improvement.
ESTHER : Kim_2021_Molecules_26_
PubMedSearch : Kim_2021_Molecules_26_
PubMedID: 34070099

Title : Multiple reactivities of flavonoids towards pathological elements in Alzheimer's disease: structure-activity relationship - Nam_2020_Chem.Sci_11_10243
Author(s) : Nam G , Hong M , Lee J , Lee HJ , Ji Y , Kang J , Baik MH , Lim MH
Ref : Chem Sci , 11 :10243 , 2020
Abstract : Amyloid-beta (Abeta) accumulation, metal ion dyshomeostasis, oxidative stress, and cholinergic deficit are four major characteristics of Alzheimer's disease (AD). Herein, we report the reactivities of 12 flavonoids against four pathogenic elements of AD: metal-free and metal-bound Abeta, free radicals, and acetylcholinesterase. A series of 12 flavonoids was selected based on the molecular structures that are responsible for multiple reactivities including hydroxyl substitution and transfer of the B ring from C2 to C3. Our experimental and computational studies reveal that the catechol moiety, the hydroxyl groups at C3 and C7, and the position of the B ring are important for instilling multiple functions in flavonoids. We establish a structure-activity relationship of flavonoids that should be useful for designing chemical reagents with multiple reactivities against the pathological factors of AD.
ESTHER : Nam_2020_Chem.Sci_11_10243
PubMedSearch : Nam_2020_Chem.Sci_11_10243
PubMedID: 34094290

Title : Dual-Purpose Inoculants and Their Effects on Corn Silage - Paradhipta_2020_Microorganisms_8_
Author(s) : Paradhipta DHV , Lee SS , Kang B , Joo YH , Lee HJ , Lee Y , Kim J , Kim SC
Ref : Microorganisms , 8 : , 2020
Abstract : This study was conducted to screen dual-purpose lactic acid bacteria (LAB) from uncontrolled farm-scale silage, and then we confirmed their effects on corn silage. The LAB were isolated from eight farm-scale corn silages, and then we screened the antifungal activity against Fusarium graminearum and the carboxylesterase activity using spectrophotometer with p-nitrophenyl octanoate as substrate and McIlvane solution as buffer. From a total of 25 isolates, 5M2 and 6M1 isolates were selected as silage inoculants because presented both activities of antifungal and carboxylesterase. According 16S rRNA gene sequencing method, 5M2 isolate had 100.0% similarity with Lactobacillus brevis, and 6M1 isolate had 99.7% similarity with L. buchneri. Corn forage was ensiled in bale silo (500 kg) for 72 d without inoculant (CON) or with mixture of selected isolates at 1:1 ratio (INO). The INO silage had higher nutrient digestibility in the rumen than CON silage. Acetate was higher and yeasts were lower in INO silage than in CON silage on the day of silo opening. In all days of aerobic exposure, yeasts were lower in INO silage than CON silage. The present study concluded that Lactobacillus brevis 5M2 and L. buchneri 6M1 confirmed antifungal and carboxylesterase activities on farm-scale corn silage.
ESTHER : Paradhipta_2020_Microorganisms_8_
PubMedSearch : Paradhipta_2020_Microorganisms_8_
PubMedID: 32443787

Title : Potential Regulatory Role of Human-Carboxylesterase-1 Glycosylation in Liver Cancer Cell Growth - Na_2020_J.Proteome.Res_19_4867
Author(s) : Na K , Kim M , Kim CY , Lim JS , Cho JY , Shin H , Lee HJ , Kang BJ , Han DH , Kim H , Baik JH , Swiatek-de Lange M , Karl J , Paik YK
Ref : J Proteome Res , 19 :4867 , 2020
Abstract : We previously reported that human carboxylesterase 1 (CES1), a serine esterase containing a unique N-linked glycosyl group at Asn79 (N79 CES1), is a candidate serological marker of hepatocellular carcinoma (HCC). CES1 is normally present at low-to-undetectable levels in normal human plasma, HCC tumors, and major liver cancer cell lines. To investigate the potential mechanism underlying the suppression of CES1 expression in liver cancer cells, we took advantage of the low detectability of this marker in tumors by overexpressing CES1 in multiple HCC cell lines, including stable Hep3B cells. We found that the population of CES1-overexpressing (OE) cells decreased and that their doubling time was longer compared with mock control liver cancer cells. Using interactive transcriptome, proteome, and subsequent Gene Ontology enrichment analysis of CES1-OE cells, we found substantial decreases in the expression levels of genes involved in cell cycle regulation and proliferation. This antiproliferative function of the N79 glycan of CES1 was further supported by quantitative real-time polymerase chain reaction, flow cytometry, and an apoptosis protein array assay. An analysis of the levels of key signaling target proteins via Western blotting suggested that CES1 overexpression exerted an antiproliferative effect via the PKD1/PKCmicro signaling pathway. Similar results were also seen in another HCC cell line (PLC/RFP/5) after transient transfection with CES1 but not in similarly treated non-HCC cell lines (e.g., HeLa and Tera-1 cells), suggesting that CES1 likely exerts a liver cell-type-specific suppressive effect. Given that the N-linked glycosyl group at Asn79 (N79 glycan) of CES1 is known to influence CES1 enzyme activity, we hypothesized that the post-translational modification of CES1 at N79 may be linked to its antiproliferative activity. To investigate the regulatory effect of the N79 glycan on cellular growth, we mutated the single N-glycosylation site in CES1 from Asn to Gln (CES1-N79Q) via site-directed mutagenesis. Fluorescence 2-D difference gel electrophoresis protein expression analysis of cell lysates revealed an increase in cell growth and a decrease in doubling time in cells carrying the N79Q mutation. Thus our results suggest that CES1 exerts an antiproliferative effect in liver cancer cells and that the single N-linked glycosylation at Asn79 plays a potential regulatory role. These functions may underlie the undetectability of CES1 in human HCC tumors and liver cancer cell lines. Mass spectrometry data are available via ProteomeXchange under the identifier PXD021573.
ESTHER : Na_2020_J.Proteome.Res_19_4867
PubMedSearch : Na_2020_J.Proteome.Res_19_4867
PubMedID: 33206527
Gene_locus related to this paper: human-CES1

Title : Lipases associated with plant defense against pathogens - Lee_2019_Plant.Sci_279_51
Author(s) : Lee HJ , Park OK
Ref : Plant Sci , 279 :51 , 2019
Abstract : When facing microbe invaders, plants activate genetic and metabolic defense mechanisms and undergo extracellular and intracellular changes to obtain a certain level of host resistance. Dynamic adjustment and adaptation occur in structures containing lipophilic compounds and cellular metabolites. Lipids encompassing fatty acids, fatty acid-based polymers, and fatty acid derivatives are part of the fundamental architecture of cells and tissues and are essential compounds in numerous biological processes. Lipid-associated plant defense responses are mostly facilitated by the activation of lipases (lipid hydrolyzing proteins), which cleave or transform lipid substrates in various subcellular compartments. In this review, several types of plant defense-associated lipases are described, including their molecular aspects, enzymatic actions, cellular functions, and possible functional relevance in plant defense. Defensive roles are discussed considering enzyme properties, lipid metabolism, downstream regulation, and phenotypic traits in loss-of-function mutants.
ESTHER : Lee_2019_Plant.Sci_279_51
PubMedSearch : Lee_2019_Plant.Sci_279_51
PubMedID: 30709493

Title : Orobol: An Isoflavone Exhibiting Regulatory Multifunctionality against Four Pathological Features of Alzheimer's Disease - Nam_2019_ACS.Chem.Neurosci_10_3386
Author(s) : Nam G , Ji Y , Lee HJ , Kang J , Yi Y , Kim M , Lin Y , Lee YH , Lim MH
Ref : ACS Chem Neurosci , 10 :3386 , 2019
Abstract : We report orobol as a multifunctional isoflavone with the ability to (i) modulate the aggregation pathways of both metal-free and metal-bound amyloid-beta, (ii) interact with metal ions, (iii) scavenge free radicals, and (iv) inhibit the activity of acetylcholinesterase. Such a framework with multifunctionality could be useful for developing chemical reagents to advance our understanding of multifaceted pathologies of neurodegenerative disorders, including Alzheimer's disease.
ESTHER : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedSearch : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedID: 31199606

Title : Ameliorating effect of Citrus aurantium extracts and nobiletin on betaamyloid (142)induced memory impairment in mice - Lee_2019_Mol.Med.Rep_20_3448
Author(s) : Lee HJ , Lee SK , Lee DR , Choi BK , Le B , Yang SH
Ref : Mol Med Rep , 20 :3448 , 2019
Abstract : The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid beta 142 (Abeta 142)induced spatial learning and memory impairment in mice. After injecting Abeta 142 (5 microl/2.5 min, intracerebroventricular injection), amnesic mice were orally administered CAE and nobiletin for 28 days. Memory, spatial and cognitive ability were measured using passive avoidance and a Morris water maze task. Acetylcholinesterase (AchE) activity was investigated in the hippocampus and cortex using commercial kits and the analysis of Bax, Bcl2, and cleaved caspase3 protein expression by western blot assays was used to confirm the antiapoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Abetainduced neurodegenerative mice with increased AchE activity in the brain. However, the daily administration of CAE and nobiletin reduced the spatial learning deficits and increased the AchE activity in the cortex and hippocampus. Furthermore, CAE and nobiletin significantly downregulated the Bax and cleaved caspase3 protein expression and upregulated the Bcl2 and Bcl2/Bax expression in the cortex and hippocampus of Abetatreated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating antiapoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.
ESTHER : Lee_2019_Mol.Med.Rep_20_3448
PubMedSearch : Lee_2019_Mol.Med.Rep_20_3448
PubMedID: 31432129

Title : Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the Last Decade - Savelieff_2019_Chem.Rev_119_1221
Author(s) : Savelieff MG , Nam G , Kang J , Lee HJ , Lee M , Lim MH
Ref : Chem Rev , 119 :1221 , 2019
Abstract : Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow a negative outlook. Although a large amount of research has been dedicated to elucidating the pathologies of neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, and neurotransmitter deficiencies are pathological features shared across multiple neurodegenerative disorders. In addition, these factors are proposed to be interrelated upon disease progression. Thus, the development of multifunctional compounds capable of simultaneously interacting with several pathological components has been suggested as a solution to undertake the complex pathologies of neurodegenerative diseases. In this review, we outline and discuss possible therapeutic targets in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis and molecules, previously designed or discovered as potential drug candidates for these disorders with emphasis on multifunctionality. In addition, underrepresented areas of research are discussed to indicate new directions.
ESTHER : Savelieff_2019_Chem.Rev_119_1221
PubMedSearch : Savelieff_2019_Chem.Rev_119_1221
PubMedID: 30095897

Title : Structural Basis of Karrikin and Non-natural Strigolactone Perception in Physcomitrella patens - Burger_2019_Cell.Rep_26_855
Author(s) : Burger M , Mashiguchi K , Lee HJ , Nakano M , Takemoto K , Seto Y , Yamaguchi S , Chory J
Ref : Cell Rep , 26 :855 , 2019
Abstract : In plants, strigolactones are perceived by the dual receptor-hydrolase DWARF14 (D14). D14 belongs to the superfamily of alpha/beta hydrolases and is structurally similar to the karrikin receptor KARRIKIN INSENSITIVE 2 (KAI2). The moss Physcomitrella patens is an ideal model system for studying this receptor family, because it includes 11 highly related family members with unknown ligand specificity. We present the crystal structures of three Physcomitrella D14/KAI2-like proteins and describe a loop-based mechanism that leads to a permanent widening of the hydrophobic substrate gorge. We have identified protein clades that specifically perceive the karrikin KAR1 and the non-natural strigolactone isomer (-)-5-deoxystrigol in a highly stereoselective manner.
ESTHER : Burger_2019_Cell.Rep_26_855
PubMedSearch : Burger_2019_Cell.Rep_26_855
PubMedID: 30673608
Gene_locus related to this paper: phypa-a9sg07 , phypa-a9skf7 , phypa-a9st85

Title : Observational Study of Clinical and Functional Progression Based on Initial Brain MRI Characteristics in Patients with Alzheimer's Disease - Choi_2018_J.Alzheimers.Dis_66_1721
Author(s) : Choi H , Yang Y , Han HJ , Jeong JH , Park MY , Kim YB , Jo KD , Choi JY , Kang KH , Kang H , Kwon DY , Yoo BG , Lee HJ , Shin BS , Jeon SM , Kwon OD , Kim JS , Lee SJ , Kim Y , Park TH , Kim YJ , Yang HJ , Park HY , Shin HE , Lee JS , Jung YH , Lee AY , Shin DI , Shin KJ , Park KH
Ref : J Alzheimers Dis , 66 :1721 , 2018
Abstract : BACKGROUND: Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established. OBJECTIVE: To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year. METHODS: In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months. RESULTS: Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline. CONCLUSION: Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status.
ESTHER : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedSearch : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedID: 30452413

Title : Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model - Han_2018_Lab.Anim.Res_34_37
Author(s) : Han SH , Kim SJ , Yun YW , Nam SY , Lee HJ , Lee BJ
Ref : Lab Anim Res , 34 :37 , 2018
Abstract : This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) (P<0.05). In the Y-maze test, the spontaneous alternation in al HLJG0711-treated groups was significantly increased compared with that in SPL-G (P<0.05). In the Morris water maze test, the escape latency and time spent in the target quadrant in all HLJG0701-treated groups were significantly decreased and increased, respectively, compared with those in SPL-G (P<0.05). In addition, the brain-derived neurotrophic factor level in groups treated with HLJG0701 300 and 600 mg/kg body weight was significantly increased compared with that in SPL-G (P<0.05). These results suggest that the HLJG0701 may protect against memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.
ESTHER : Han_2018_Lab.Anim.Res_34_37
PubMedSearch : Han_2018_Lab.Anim.Res_34_37
PubMedID: 29628975

Title : Lactobacillus johnsonii CJLJ103 Attenuates Scopolamine-Induced Memory Impairment in Mice by Increasing BDNF Expression and Inhibiting NF-kappaB Activation - Lee_2018_J.Microbiol.Biotechnol_28_1443
Author(s) : Lee HJ , Lim SM , Kim DH
Ref : J Microbiol Biotechnol , 28 :1443 , 2018
Abstract : In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed TNF-alpha expression and NF-kappaB activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited NF-kappaB activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting NF-kappaB activation.
ESTHER : Lee_2018_J.Microbiol.Biotechnol_28_1443
PubMedSearch : Lee_2018_J.Microbiol.Biotechnol_28_1443
PubMedID: 30111074

Title : Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling - Jeon_2017_Neuropharmacol_113_100
Author(s) : Jeon SJ , Lee HJ , Lee HE , Park SJ , Gwon Y , Kim H , Zhang J , Shin CY , Kim DH , Ryu JH
Ref : Neuropharmacology , 113 :100 , 2017
Abstract : Oleanolic acid is a naturally occurring triterpenoid and is widely present in food and medicinal plants. To examine the effect of oleanolic acid on memory deficits, we employed a cholinergic blockade-induced cognitive deficit mouse model. A single administration of oleanolic acid significantly increased the latency on the passive avoidance task and affected the alternation behavior on the Y-maze task and the exploration time on the novel object recognition task, indicating that oleanolic acid reverses the cognitive impairment induced by scopolamine. In accordance with previous reports, oleanolic acid enhanced extracellular-signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Interestingly, ameliorating effect of oleanolic acid on scopolamine-induced memory impairment was abolished by N2-(2-{[(2-oxoazepan-3-yl)amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide (ANA-12), a potent and specific inhibitor of tropomyosin receptor kinase B (TrkB), in the passive avoidance task. Similarly, oleanolic acid significantly evoked long-term potentiation in a dose-dependent manner, which was diminished by ANA-12 treatment as shown in the electrophysiology study. Together, these results imply that oleanolic acid ameliorates scopolamine-induced memory impairment by modulating the BDNF-ERK1/2-CREB pathway through TrkB activation in mice, suggesting that oleanolic acid would be a potential therapeutic agent for the treatment of cognitive deficits.
ESTHER : Jeon_2017_Neuropharmacol_113_100
PubMedSearch : Jeon_2017_Neuropharmacol_113_100
PubMedID: 27470063

Title : Development of an antibody-based diagnostic method for the identification of Bemisia tabaci biotype B - Baek_2016_Pestic.Biochem.Physiol_131_18
Author(s) : Baek JH , Lee HJ , Kim YH , Lim KJ , Lee SH , Kim BJ
Ref : Pestic Biochem Physiol , 131 :18 , 2016
Abstract : The whitefly Bemisia tabaci is a very destructive pest. B. tabaci is composed of various morphologically undistinguishable biotypes, among which biotypes B and Q, in particular, draw attention because of their wide distribution in Korea and differential potentials for insecticide resistance development. To develop a biotype-specific protein marker that can readily distinguishes biotypes B from other biotypes in the field, we established an ELISA protocol based on carboxylesterase 2 (COE2), which is more abundantly expressed in biotypes B compared with Q. Recombinant COE2 was expressed, purified and used for antibody construction. Polyclonal antibodies specific to B. tabaci COE2 [anti-COE2 pAb and deglycosylated anti-COE2 pAb (DG anti-COE2 pAb)] revealed a 3-9-fold higher reactivity to biotype B COE2 than biotype Q COE2 by Western blot and ELISA analyses. DG anti-COE2 pAb exhibited low non-specific activity, demonstrating its compatibility in diagnosing biotypes. Western blot and ELISA analyses determined that one of the 11 field populations examined was biotype B and the others were biotype Q, suggesting the saturation of biotype Q in Korea. DG anti-COE2 pAb discriminates B. tabaci biotypes B and Q with high specificity and accuracy and could be useful for the development of a B. tabaci biotype diagnosis kit for on-site field applications.
ESTHER : Baek_2016_Pestic.Biochem.Physiol_131_18
PubMedSearch : Baek_2016_Pestic.Biochem.Physiol_131_18
PubMedID: 27265822

Title : Tumor-specific gene therapy for pancreatic cancer using human neural stem cells encoding carboxylesterase - Choi_2016_Oncotarget_7_75319
Author(s) : Choi SS , Yoon K , Choi SA , Yoon SB , Kim SU , Lee HJ
Ref : Oncotarget , 7 :75319 , 2016
Abstract : Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT-11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer.
ESTHER : Choi_2016_Oncotarget_7_75319
PubMedSearch : Choi_2016_Oncotarget_7_75319
PubMedID: 27659534

Title : Internal Concentration and Time Are Important Modifiers of Toxicity: The Case of Chlorpyrifos on Caenorhabditis elegans - Roh_2016_Environ.Sci.Technol_50_9689
Author(s) : Roh JY , Lee HJ , Kwon JH
Ref : Environ Sci Technol , 50 :9689 , 2016
Abstract : The internal concentration of chemicals in exposed organisms changes over time due to absorption, distribution, metabolism, and excretion processes since chemicals are taken up from the environment. Internal concentration and time are very important modifiers of toxicity when biomarkers are used to evaluate the potential hazards and risks of environmental pollutants. In this study, the responses of molecular biomarkers, and the fate of chemicals in the body, were comprehensively investigated to determine cause-and-effect relationships over time. Chlorpyrifos (CP) was selected as a model chemical, and Caenorhabditis elegans was exposed to CP for 4 h using the passive dosing method. Worms were then monitored in fresh medium during a 48-h recovery regime. The mRNA expression of genes related to CYP metabolism (cyp35a2 and cyp35a3) increased during the constant exposure phase. The body residue of CP decreased once it reached a peak level during the early stage of exposure, indicating that the initial uptake of CP rapidly induced biotransformation with the synthesis of new CYP metabolic proteins. The residual chlorpyrifos-oxon concentration, an acetylcholinesterase (AChE) inhibitor, continuously increased even after the recovery regime started. These delayed toxicokinetics seem to be important for the extension of AChE inhibition for up to 9 h after the start of the recovery regime. Comprehensive investigation into the molecular initiation events and changes in the internal concentrations of chemical species provide insight into response causality within the framework of an adverse outcome pathway.
ESTHER : Roh_2016_Environ.Sci.Technol_50_9689
PubMedSearch : Roh_2016_Environ.Sci.Technol_50_9689
PubMedID: 27490261

Title : Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice - Kim_2016_BMC.Complement.Altern.Med_16_66
Author(s) : Kim J , Shim J , Lee S , Cho WH , Hong E , Lee JH , Han JS , Lee HJ , Lee KW
Ref : BMC Complement Altern Med , 16 :66 , 2016
Abstract : BACKGROUND: Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice.
METHODS: Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1-14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-kappaB (NF-kappaB) in the hippocampus were also examined.
RESULTS: Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-kappaB pathway (i.e., phosphorylation of p65) in the hippocampus. CONCLUSION: These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-kappaB signaling in the hippocampus.
ESTHER : Kim_2016_BMC.Complement.Altern.Med_16_66
PubMedSearch : Kim_2016_BMC.Complement.Altern.Med_16_66
PubMedID: 26887326

Title : Human Neural Stem Cells Overexpressing a Carboxylesterase Inhibit Bladder Tumor Growth - Choi_2016_Mol.Cancer.Ther_15_1201
Author(s) : Choi SS , Chi BH , Chang IH , Kim KD , Lee SR , Kim SU , Lee HJ
Ref : Mol Cancer Ther , 15 :1201 , 2016
Abstract : Bladder cancer is a significant clinical and economic problem. Despite intravesical chemotherapy and immunotherapy, up to 80% of patients with non-muscle-invasive bladder cancer develop recurrent tumors, of which 20% to 30% evolve into more aggressive, potentially lethal tumors. Recently, bladder cancer cells are considered to be mediators of resistance to current therapies and therefore represent strong candidates as biologic targets. No effective chemotherapy has yet been developed for advanced bladder cancer. It is desirable that a drug can be delivered directly and specifically to bladder cancer cells. Stem cells have selective migration ability toward cancer cells, and therapeutic genes can be easily transduced into stem cells. In suicide gene therapy for cancer, stem cells carry a gene encoding a carboxylesterase (CE) enzyme that transforms an inert CPT-11 prodrug into a toxic SN-38 product, a topoisomerase 1 inhibitor. In immunodeficient mice, systemically transplanted HB1.F3.CE stem cells migrated toward the tumor implanted by the TCCSUP bladder cancer cell line, and, in combination with CPT-11, the volume of tumors was significantly reduced. These findings may contribute to the development of a new selective chemotherapeutic strategy against bladder cancer. Mol Cancer Ther; 15(6); 1201-7. (c)2016 AACR.
ESTHER : Choi_2016_Mol.Cancer.Ther_15_1201
PubMedSearch : Choi_2016_Mol.Cancer.Ther_15_1201
PubMedID: 27009215

Title : Effects of donepezil on hERG potassium channels - Chae_2015_Brain.Res_1597_77
Author(s) : Chae YJ , Lee HJ , Jeon JH , Kim IB , Choi JS , Sung KW , Hahn SJ
Ref : Brain Research , 1597 :77 , 2015
Abstract : Donepezil is a potent, selective inhibitor of acetylcholinesterase, which is used for the treatment of Alzheimer's disease. Whole-cell patch-clamp technique and Western blot analyses were used to study the effects of donepezil on the human ether-a-go-go-related gene (hERG) channel. Donepezil inhibited the tail current of the hERG in a concentration-dependent manner with an IC50 of 1.3muM. The metabolites of donepezil, 6-ODD and 5-ODD, inhibited the hERG currents in a similar concentration-dependent manner; the IC50 values were 1.0 and 1.5muM, respectively. A fast drug perfusion system demonstrated that donepezil interacted with both the open and inactivated states of the hERG. A fast application of donepezil during the tail currents inhibited the open state of the hERG in a concentration-dependent manner with an IC50 of 2.7muM. Kinetic analysis of donepezil in an open state of the hERG yielded blocking and unblocking rate constants of 0.54microM(-1)s(-1) and 1.82s(-1), respectively. The block of the hERG by donepezil was voltage-dependent with a steep increase across the voltage range of channel activation. Donepezil caused a reduction in the hERG channel protein trafficking to the plasma membrane at low concentration, but decreased the channel protein expression at higher concentrations. These results suggest that donepezil inhibited the hERG at a supratherapeutic concentration, and that it did so by preferentially binding to the activated (open and/or inactivated) states of the channels and by inhibiting the trafficking and expression of the hERG channel protein in the plasma membrane.
ESTHER : Chae_2015_Brain.Res_1597_77
PubMedSearch : Chae_2015_Brain.Res_1597_77
PubMedID: 25498859

Title : Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats - Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
Author(s) : Lee B , Sur BJ , Han JJ , Shim I , Her S , Lee YS , Lee HJ , Hahm DH
Ref : Prog Neuropsychopharmacol Biological Psychiatry , 56C :1 , 2014
Abstract : Recently, lecithin-derived phosphatidylserine (PS), which originates from marine life, has received much attention as a viable alternative to bovine cerebral cortex PS. In this study, the use of squid phosphatidylcholine-transphosphatidylated PS (SQ-PS) was evaluated through examination of its ameliorating effects on age-associated learning and memory deficits in rats. Aged rats were orally administered SQ-PS (10, 20, or 50mg/kg per day) once a day for seven days 30min prior to behavioral assessment in a Morris water maze. SQ-PS administration produced significant dose-dependent improvements in escape latency for finding the platform in the Morris water maze in the aged rats even though Soy-PS administration also exhibited comparable improvements with SQ-PS. Biochemical alterations in the hippocampal cholinergic system, including changes in choline acetyltransferase and acetylcholinesterase immunoreactivity, were consistent with the behavioral results. In addition, SQ-PS treatment significantly restored age-associated decreases of choline transporter and muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus. These results demonstrate that orally administered SQ-PS dose-dependently aids in the improvement of memory deficits that occur during normal aging in rats. This suggests that SQ-PS may be a useful therapeutic agent in the treatment of diminished memory function in elderly people.
ESTHER : Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
PubMedSearch : Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
PubMedID: 25058912

Title : Ramlibacter solisilvae sp. nov., isolated from forest soil, and emended description of the genus Ramlibacter - Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
Author(s) : Lee HJ , Lee SH , Lee SS , Lee JS , Kim Y , Kim SC , Jeon CO
Ref : Int J Syst Evol Microbiol , 64 :1317 , 2014
Abstract : A Gram-staining-negative, strictly aerobic, white-colony-forming bacterium, designated strain 5-10(T), was isolated from forest soil of Bac Kan Province in Vietnam. Cells were non-motile rods or coccoids, showing oxidase- and catalase-positive reactions. Growth was observed at 10-37 degrees C (optimum, 30 degrees C), at pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids were summed feature 3 (comprising C16 : 1omega6c and/or C16 : 1omega7c), C16 : 0, C10 : 0 3-OH and summed feature 8 (comprising C18 : 1omega6c and/or C18 : 1omega7c). The G+C content of the genomic DNA was 69.9 mol% and the only respiratory quinone detected was ubiquinone 8 (Q-8). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 5-10(T) formed a tight phyletic lineage with members of the genus Ramlibacter. Strain 5-10(T) was most closely related to Ramlibacter tataouinensis TTB310(T) (97.3 %), but the DNA-DNA relatedness level between the two strains was 38.2+/-1.8 %. Based on phenotypic, chemotaxonomic and molecular features, strain 5-10(T) was shown to represent a novel species of the genus Ramlibacter, for which the name Ramlibacter solisilvae sp. nov. is proposed. The type strain is 5-10(T) ( = KACC 17567(T) = JCM 19319(T)). An emended description of the genus Ramlibacter is also proposed.
ESTHER : Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
PubMedSearch : Lee_2014_Int.J.Syst.Evol.Microbiol_64_1317
PubMedID: 24425747
Gene_locus related to this paper: 9burk-a0a127juv8

Title : Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59 - Lee_2012_J.Bacteriol_194_544
Author(s) : Lee SH , Jin HM , Lee HJ , Kim JM , Jeon CO
Ref : Journal of Bacteriology , 194 :544 , 2012
Abstract : Pseudoxanthomonas spadix BD-a59, able to metabolize all six BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p-xylene) compounds, was isolated from gasoline-contaminated sediment. Here, we report the complete 3.45-Mb genome sequence and annotation of strain BD-a59. These advance the understanding of strain BD-a59's genomic properties and pollutant metabolic versatility.
ESTHER : Lee_2012_J.Bacteriol_194_544
PubMedSearch : Lee_2012_J.Bacteriol_194_544
PubMedID: 22207748
Gene_locus related to this paper: pseup-g7unl8 , pseup-g7uu78

Title : Proteomics-based identification and characterization of biotype-specific carboxylesterase 2 putatively associated with insecticide resistance in Bemisia tabaci - Kang_2012_J.Asia.Pac.Entomol_15_389
Author(s) : Kang S , Lee HJ , Kim YH , Kwon DH , Oh JH , Kim BJ , Lim KJ , Lee S , Hwang SY , Lee SH
Ref : Journal of Asia-Pacific Entomology , 15 :389 , 2012
Abstract : Proteomic differences between Bemisia tabaci biotypes (B and Q) were investigated by two-dimensional gel electrophoresis in conjunction with mass spectroscopic analysis. Among several protein spots specific to biotype B, carboxylesterase 2 (Coe2) was significantly more expressed in biotype B. Phylogenetic analysis demonstrated the close relationship of Coe2 with Myzus persicae esterase E4. Comparison of full-length cDNA sequences of Coe2 revealed no amino acid differences in functionally important conserved regions between biotypes B and Q. The transcription level of the Coe2 gene (coe2) was 5.8-fold higher in biotype B than in biotype Q, but the coe2 copy number was not different between biotypes, suggesting that the overexpression of Coe2 was due to transcriptional up-regulation. Native isoelectric focusing followed by mass spectrophotometric analysis confirmed that the overexpressed pI 5.7 esterase in biotype B was Coe2. In-gel inhibition of Coe2 by three insecticides indicated the interaction of Coe2 with chlorpyrifos-methyl oxon and permethrin, but not with imidacloprid. These findings suggest that overexpression of Coe2 in biotype B can confer chemical defense against pyrethroid and organophosphate insecticides, perhaps by sequestration and hydrolysis, as seen in M. persicae E4. Finally, utility of Coe2 as a potential biotype-specific protein marker is discussed.
ESTHER : Kang_2012_J.Asia.Pac.Entomol_15_389
PubMedSearch : Kang_2012_J.Asia.Pac.Entomol_15_389

Title : One-step identification of B and Q biotypes of Bemisia tabaci based on intron variation of carboxylesterase 2 - Kang_2012_J.Asia.Pac.Entomol_15_383
Author(s) : Kang S , Kim YH , Lee HJ , Kim BJ , Lim KJ , Lee SH
Ref : Journal of Asia-Pacific Entomology , 15 :383 , 2012
Abstract : Sequence and length-polymorphic intron variations in the caboxylesterase 2 gene (coe2) were determined to be specific to the biotypes B and Q of Bemisia tabaci. By employing the biotype-specific coe2 intron variation as a nuclear marker, a one-step diagnostic protocol for the identification of B and Q biotypes was developed and its performance was validated for field collected B. tabaci specimens. The diagnostic results based on the coe2 intron marker were identical to those obtained from the mtCOI marker in all 256 specimens examined except for four individuals that appeared to be putative heterozygotes between B and Q biotypes. These results demonstrate a high level of accuracy of the coe2 intron marker-based protocol in distinguishing biotypes B and Q. Moreover, because the process requires only PCR amplification and gel electrophoresis, analysis of multiple samples can be done more efficiently. Based on the observation that all putative heterozygotes have the maternal background of Q biotype, they may have been created by inter-biotype cross between B type male and Q type female. If combined with the mtCOI marker, the nuclear coe2 marker would provide a better resolution than maternally inherited markers alone and facilitate the demographic study of B. tabaci biotype complex.
ESTHER : Kang_2012_J.Asia.Pac.Entomol_15_383
PubMedSearch : Kang_2012_J.Asia.Pac.Entomol_15_383

Title : FrsA functions as a cofactor-independent decarboxylase to control metabolic flux - Lee_2011_Nat.Chem.Biol_7_434
Author(s) : Lee KJ , Jeong CS , An YJ , Lee HJ , Park SJ , Seok YJ , Kim P , Lee JH , Lee KH , Cha SS
Ref : Nat Chemical Biology , 7 :434 , 2011
Abstract : The interaction between fermentation-respiration switch (FrsA) protein and glucose-specific enzyme IIA(Glc) increases glucose fermentation under oxygen-limited conditions. We show that FrsA converts pyruvate to acetaldehyde and carbon dioxide in a cofactor-independent manner and that its pyruvate decarboxylation activity is enhanced by the dephosphorylated form of IIA(Glc) (d-IIA(Glc)). Crystal structures of FrsA and its complex with d-IIA(Glc) revealed residues required for catalysis as well as the structural basis for the activation by d-IIA(Glc).
ESTHER : Lee_2011_Nat.Chem.Biol_7_434
PubMedSearch : Lee_2011_Nat.Chem.Biol_7_434
PubMedID: 21623357
Gene_locus related to this paper: vibvy-y856

Title : Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase - Lim_2011_Cancer.Gene.Ther_18_817
Author(s) : Lim SH , Choi SA , Lee JY , Wang KC , Phi JH , Lee DH , Song SH , Song JH , Jin X , Kim H , Lee HJ , Lim I , Kim SU , Kim SK
Ref : Cancer Gene Therapy , 18 :817 , 2011
Abstract : The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, P<0.001) or CPT-11 only (median survival: 118 days, P<0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.
ESTHER : Lim_2011_Cancer.Gene.Ther_18_817
PubMedSearch : Lim_2011_Cancer.Gene.Ther_18_817
PubMedID: 21869821

Title : Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats - Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
Author(s) : Lee B , Sur BJ , Han JJ , Shim I , Her S , Lee HJ , Hahm DH
Ref : Prog Neuropsychopharmacol Biological Psychiatry , 34 :1085 , 2010
Abstract : The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on the learning and memory deficits associated with normal aging in rats was investigated, as compared with soybean PS (SOY-PS). Rats were orally administered with KR-PS (20, 50 mg kg-1) and SOY-PS (50 mg kg-1) daily, for 7 days, 30 min before behavioral assessment using the Morris water maze (MWM). Changes in the cholinergic system were examined by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily administration of KR-PS produced a significant improvement in the escape latency for finding the platform in the MWM, as compared with SOY-PS. Consistent with the behavioral results, KR-PS treatments significantly alleviated age-associated losses of cholinergic immunoreactivity, and muscarinic acetylcholine receptor type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the hippocampus. These findings demonstrate that KR-PS showed significant neuroprotective activity against the neuronal and cognitive impairments that occur with normal aging in rats; comparable results were obtained with SOY-PS. These data indicate that oral administration of PS derived from marine life could substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement of diminished memory function in elderly people.
ESTHER : Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
PubMedSearch : Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
PubMedID: 20677367

Title : Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus - Lee_2010_J.Pharm.Pharmacol_62_263
Author(s) : Lee B , Park J , Kwon S , Park MW , Oh SM , Yeom MJ , Shim I , Lee HJ , Hahm DH
Ref : J Pharm Pharmacol , 62 :263 , 2010
Abstract : OBJECTIVES: The ameliorating effects of wild ginseng on learning and memory deficits were investigated in rats. METHODS: Rats were treated daily with wild ginseng or cultivated ginseng for 7 days at 30 min before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment by the administration of scopolamine, behavioural assessment using the Morris water maze was performed. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase and the reactivity of acetylcholinesterase in the hippocampus. KEY FINDINGS: Scopolamine injection induced impaired performance in the water maze test and severe cell losses in hippocampal cholinergic neurons, as indicated by decreased choline acetyltransferase immunoreactivity and increased acetylcholinesterase reactivity. Daily administration of wild ginseng produced a significant improvement in the escape latency for finding the platform in the Morris water maze and reduced the loss of cholinergic immunoreactivity in the hippocampus. The reduced expression of brain-derived neurotrophic factor mRNA due to the scopolamine injection was recovered to normal levels by the administration of wild ginseng. CONCLUSIONS: Wild ginseng demonstrates a significant neuroprotective effect against scopolamine-induced neuronal and cognitive impairment.
ESTHER : Lee_2010_J.Pharm.Pharmacol_62_263
PubMedSearch : Lee_2010_J.Pharm.Pharmacol_62_263
PubMedID: 20487207

Title : Naturally occurring phytochemicals for the prevention of Alzheimer's disease - Kim_2010_J.Neurochem_112_1415
Author(s) : Kim J , Lee HJ , Lee KW
Ref : Journal of Neurochemistry , 112 :1415 , 2010
Abstract : Alzheimer's disease (AD) is an age-related neurodegenerative disease increasingly recognized as one of the most important medical problems affecting the elderly. Although a number of drugs, including several cholinesterase inhibitors and an NMDA receptor antagonist, have been approved for use, they have been shown to produce diverse side effects and yield relatively modest benefits. To overcome these limitations of current therapeutics for AD, extensive research and development are underway to identify drugs that are effective and free of undesirable side effects. Certain naturally occurring dietary polyphenolic phytochemicals have received considerable recent attention as alternative candidates for AD therapy. In particular, curcumin, resveratrol, and green tea catechins have been suggested to have the potential to prevent AD because of their anti-amyloidogenic, anti-oxidative, and anti-inflammatory properties. These polyphenolic phytochemicals also activate adaptive cellular stress responses, called 'neurohormesis', and suppress disease processes. In this commentary, we describe the amyloid-beta-induced pathogenesis of AD, and summarize the intracellular and molecular targets of selected dietary phytochemicals that might slow the progression of AD.
ESTHER : Kim_2010_J.Neurochem_112_1415
PubMedSearch : Kim_2010_J.Neurochem_112_1415
PubMedID: 20050972

Title : Polymer nanoassemblies for cancer treatment and imaging - Lee_2010_Ther.Deliv_1_803
Author(s) : Lee HJ , Ponta A , Bae Y
Ref : Ther Deliv , 1 :803 , 2010
Abstract : Amphiphilic polymers represented by block copolymers self-assemble into well-defined nanostructures capable of incorporating therapeutics. Polymer nanoassemblies currently developed for cancer treatment and imaging are reviewed in this article. Particular attention is paid to three representative polymer nanoassemblies: polymer micelles, polymer micellar aggregates and polymer vesicles. Rationales, design and performance of these polymer nanoassemblies are addressed, focusing on increasing the solubility and chemical stability of drugs. Also discussed are polymer nanoassembly formation, the distribution of polymer materials in the human body and applications of polymer nanoassemblies for combined therapy and imaging of cancer. Updates on tumor-targeting approaches, based on preclinical and clinical results are provided, as well as solutions for current issues that drug-delivery systems have, such as in vivo stability, tissue penetration and therapeutic efficacy. These are discussed to provide insights on the future development of more effective polymer nanoassemblies for the delivery of therapeutics in the body.
ESTHER : Lee_2010_Ther.Deliv_1_803
PubMedSearch : Lee_2010_Ther.Deliv_1_803
PubMedID: 22834015

Title : Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma - Na_2009_Proteomics_9_3989
Author(s) : Na K , Lee EY , Lee HJ , Kim KY , Lee H , Jeong SK , Jeong AS , Cho SY , Kim SA , Song SY , Kim KS , Cho SW , Kim H , Paik YK
Ref : Proteomics , 9 :3989 , 2009
Abstract : To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed N-linked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.
ESTHER : Na_2009_Proteomics_9_3989
PubMedSearch : Na_2009_Proteomics_9_3989
PubMedID: 19658107
Gene_locus related to this paper: human-CES1

Title : Interactions of acetylcholinesterase with caveolin-1 and subsequently with cytochrome c are required for apoptosome formation - Park_2008_Carcinogenesis_29_729
Author(s) : Park SE , Jeong SH , Yee SB , Kim TH , Soung YH , Ha NC , Kim ND , Park JY , Bae HR , Park BS , Lee HJ , Yoo YH
Ref : Carcinogenesis , 29 :729 , 2008
Abstract : Acetylcholinesterase (AChE) is emerging as an important component in leading to apoptosis. Our previous study demonstrated that silencing of the AChE gene blocked the interaction between cytochrome c and apoptotic protease-activating factor-1 (Apaf-1) in etoposide-induced apoptosis of HT-29 cells. We undertook this study to further dissect the molecular role of AChE in apoptosome formation. The present study elicited that small interfering RNA (siRNA) to cytochrome c gene blocked the interaction of AChE with Apaf-1, whereas siRNA to Apaf-1 gene did not block the interaction of AChE with cytochrome c, indicating that the interaction of AChE with cytochrome c is required for the interaction between cytochrome c and protease-activating factor-1. We further observed that AChE is localized to caveolae via interacting with caveolin-1 during apoptosis and that the disruption of caveolae prevented apoptosome formation. These data indicate that the interactions of AChE with caveolin-1 and subsequently with cytochrome c appear to be indispensable for apoptosome formation.
ESTHER : Park_2008_Carcinogenesis_29_729
PubMedSearch : Park_2008_Carcinogenesis_29_729
PubMedID: 18258603

Title : Substituted pyrrolidine-2,4-dicarboxylic acid amides as potent dipeptidyl peptidase IV inhibitors - Tsai_2006_Bioorg.Med.Chem.Lett_16_3268
Author(s) : Tsai TY , Coumar MS , Hsu T , Hsieh HP , Chien CH , Chen CT , Chang CN , Lo YK , Wu SH , Huang CY , Huang YW , Wang MH , Wu HY , Lee HJ , Chen X , Chao YS , Jiaang WT
Ref : Bioorganic & Medicinal Chemistry Lett , 16 :3268 , 2006
Abstract : A series of substituted pyrrolidine-2,4-dicarboxylic acid amides were synthesized as potential antidiabetic agents, and many of them showed good in vitro DPP-IV inhibition (IC50 = 2-250 nM) with selectivity over DPP-II, DPP8, and FAP enzymes. Selected compounds 8c and 11a showed in vivo plasma DPP-IV inhibition after oral administration in Wistar rats.
ESTHER : Tsai_2006_Bioorg.Med.Chem.Lett_16_3268
PubMedSearch : Tsai_2006_Bioorg.Med.Chem.Lett_16_3268
PubMedID: 16581245

Title : Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8 - Lee_2006_J.Biol.Chem_281_38653
Author(s) : Lee HJ , Chen YS , Chou CY , Chien CH , Lin CH , Chang GG , Chen X
Ref : Journal of Biological Chemistry , 281 :38653 , 2006
Abstract : DPP8 belongs to the family of prolyl dipeptidases, which are capable of cleaving the peptide bond after a penultimate proline residue. Unlike DPP-IV, a drug target for type II diabetes, no information is available on the crystal structure of DPP8, the regulation of its enzymatic activity, or its substrate specificity. In this study, using analytical ultracentrifugation and native gel electrophoresis, we show that the DPP8 protein is predominantly dimeric when purified or in the cell extracts. Four conserved residues in the C-terminal loop of DPP8 (Phe(822), Val(833), Tyr(844), and His(859)), corresponding to those located at the dimer interface of DPP-IV, were individually mutated to Ala. Surprisingly, unlike DPP-IV, these single-site mutations abolished the enzymatic activity of DPP8 without disrupting its quaternary structure, indicating that dimerization itself is not sufficient for the optimal enzymatic activity of DPP8. Moreover, these mutations not only decreased k(cat), as did the corresponding DPP-IV mutations, but also dramatically increased K(m). We further show that the K(m) effect is independent of the substrate assayed. Finally, we identified the distinctive and strict substrate selectivity of DPP8 for hydrophobic or basic residues at the P2 site, which is in sharp contrast to the much less discriminative substrate specificity of DPP-IV. Our study has identified the residues absolutely required for the optimal activity of DPP8 and its unique substrate specificity. This study extends the functional importance of the C-terminal loop to the whole family of prolyl dipeptidases.
ESTHER : Lee_2006_J.Biol.Chem_281_38653
PubMedSearch : Lee_2006_J.Biol.Chem_281_38653
PubMedID: 17040910
Gene_locus related to this paper: human-DPP8

Title : The genome sequence of the ethanologenic bacterium Zymomonas mobilis ZM4 - Seo_2005_Nat.Biotechnol_23_63
Author(s) : Seo JS , Chong H , Park HS , Yoon KO , Jung C , Kim JJ , Hong JH , Kim H , Kim JH , Kil JI , Park CJ , Oh HM , Lee JS , Jin SJ , Um HW , Lee HJ , Oh SJ , Kim JY , Kang HL , Lee SY , Lee KJ , Kang HS
Ref : Nat Biotechnol , 23 :63 , 2005
Abstract : We report the complete genome sequence of Zymomonas mobilis ZM4 (ATCC31821), an ethanologenic microorganism of interest for the production of fuel ethanol. The genome consists of 2,056,416 base pairs forming a circular chromosome with 1,998 open reading frames (ORFs) and three ribosomal RNA transcription units. The genome lacks recognizable genes for 6-phosphofructokinase, an essential enzyme in the Embden-Meyerhof-Parnas pathway, and for two enzymes in the tricarboxylic acid cycle, the 2-oxoglutarate dehydrogenase complex and malate dehydrogenase, so glucose can be metabolized only by the Entner-Doudoroff pathway. Whole genome microarrays were used for genomic comparisons with the Z. mobilis type strain ZM1 (ATCC10988) revealing that 54 ORFs predicted to encode for transport and secretory proteins, transcriptional regulators and oxidoreductase in the ZM4 strain were absent from ZM1. Most of these ORFs were also found to be actively transcribed in association with ethanol production by ZM4.
ESTHER : Seo_2005_Nat.Biotechnol_23_63
PubMedSearch : Seo_2005_Nat.Biotechnol_23_63
PubMedID: 15592456
Gene_locus related to this paper: zymmo-DLH , zymmo-GAA , zymmo-metx , zymmo-q5nkz4 , zymmo-q5nmh0 , zymmo-q5nmm8 , zymmo-q5nmn0 , zymmo-q5nmz5 , zymmo-q5nnu4 , zymmo-q5npe2 , zymmo-q5nph2 , zymmo-q5npn6 , zymmo-q5nq91 , zymmo-q5nrh7 , zymmo-q5nnr5

Title : Tactile assessment for the reversibility of rocuronium-induced neuromuscular blockade during propofol or sevoflurane anesthesia - Kim_2004_Anesth.Analg_99_1080
Author(s) : Kim KS , Cheong MA , Lee HJ , Lee JM
Ref : Anesthesia & Analgesia , 99 :1080 , 2004
Abstract : We sought to determine whether tactile train-of-four (TOF) count can predict the efficacy of neostigmine administration for rocuronium-induced blockade during propofol or sevoflurane anesthesia, and to follow subsequent recovery until the TOF ratio reached 0.9. One-hundred-sixty patients, divided into eight equal groups, were randomly allocated to maintenance of anesthesia with propofol or sevoflurane. The tactile response of the adductor pollicis to TOF stimulation was evaluated on one arm, and the mechanomyographic response was recorded on the other. Neuromuscular block was induced with rocuronium 0.6 mg/kg and maintained with rocuronium to 15% of the control first twitch in TOF. Neostigmine 0.07 mg/kg was administered on reappearance of the first (Group I), second (Group II), third (Group III), or fourth (Group IV) tactile TOF response in each anesthesia. At this time, sevoflurane or the propofol dosage was reduced in each group (n = 20 in each group). The times from administration of neostigmine until the TOF ratio recovered to 0.7, 0.8, and 0.9 were recorded. The times [median (range)] to TOF ratio = 0.9 were 8.6 (4.7-18.9), 7.5 (3.4-9.8), 5.4 (1.6-8.6), and 4.7 (1.3-7.2) min in Groups I-IV during propofol anesthesia, respectively, and 28.6 (8.8-75.8), 22.6 (8.3-57.4), 15.6 (7.3-43.9), and 9.7 (5.1-26.4) min in corresponding groups during sevoflurane anesthesia, respectively (P < 0.0001). We recommend more than 2 TOF responses with propofol anesthesia and 4 TOF responses with sevoflurane anesthesia for adequate reversal within 10 and 15 min, respectively. The more tactile TOF responses present at the time of reversal achieved greater adequate recovery; however, tactile TOF responses are not a completely reliable predictor within a reasonable time period.
ESTHER : Kim_2004_Anesth.Analg_99_1080
PubMedSearch : Kim_2004_Anesth.Analg_99_1080
PubMedID: 15385354

Title : Effects of methanol extract of Uncariae Ramulus et Uncus on ibotenic acid-induced amnesia in the rat - Kim_2004_J.Pharmacol.Sci_96_314
Author(s) : Kim JH , Chung JY , Lee YJ , Park S , Hahm DH , Lee HJ , Shim I
Ref : J Pharmacol Sci , 96 :314 , 2004
Abstract : In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer's disease.
ESTHER : Kim_2004_J.Pharmacol.Sci_96_314
PubMedSearch : Kim_2004_J.Pharmacol.Sci_96_314
PubMedID: 15557736

Title : Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus - Shim_2003_Neurosurgery_53_416
Author(s) : Shim I , Ha Y , Chung JY , Lee HJ , Yang KH , Chang JW
Ref : Neurosurgery , 53 :416 , 2003
Abstract : OBJECTIVE: The septohippocampal cholinergic (SHC) system plays an important role in the maintenance of normal memory and learning. However, the fact that memory and learning impairments under hydrocephalic conditions are directly related to the SHC system is less well known. We investigated the relationships between pathological changes in SHC neurons and impairments in memory and learning among hydrocephalic rats.
METHODS: Rats with kaolin-induced hydrocephalus were prepared with injections of kaolin suspension into the cisterna magna. Learning and memory performance was assessed with the passive avoidance and Morris water maze tests. Ventricular sizes were measured for the lateral and third ventricles. Acetylcholinesterase and choline acetyltransferase immunostaining was performed to investigate degenerative changes in cholinergic neurons in the medial septum and hippocampus.
RESULTS: Hydrocephalic rats demonstrated significant learning and memory impairments in the passive avoidance and Morris water maze tests. Decreased hesitation times in the passive avoidance test and markedly increased acquisition times and decreased retention times in the Morris water maze test indicated learning and memory dysfunction among the hydrocephalic rats. The numbers of cholinergic neurons in the medial septum and hippocampus were decreased in the hydrocephalic rats. The decreases in choline acetyltransferase and acetylcholinesterase immunoreactivity were significantly correlated with enlargement of the ventricles. CONCLUSION: Impairment of spatial memory and learning may be attributable to degeneration of SHC neurons. These results suggest that learning and memory impairments in rats with kaolin-induced hydrocephalus are associated with the dysfunction of the SHC system induced by ventricular dilation.
ESTHER : Shim_2003_Neurosurgery_53_416
PubMedSearch : Shim_2003_Neurosurgery_53_416
PubMedID: 12925261

Title : First-order kinetics analysis of monomer composition dependent polyhydroxyalkanoic acid degradation in Pseudomonas spp - Choi_2003_Biomacromolecules_4_424
Author(s) : Choi MH , Rho JK , Lee HJ , Song JJ , Yoon SC , Lee SY
Ref : Biomacromolecules , 4 :424 , 2003
Abstract : The intracellular degradation of polyhydroxyalkanoic acid (PHA) in pseudomonads was investigated by first-order kinetics analysis using the initial rate method. One type of PHA was accumulated in five Pseudomonas spp., P. oleovorans, P. aeruginosa, P. fluorescens, P. citronellolis, and P. putida, by growing them on octanoic acid. The monomer compositions of the five PHA were not significantly different from one another: 85-90 mol % 3-hydroxyoctanoic acid (3HO), 7-12 mol % 3-hydorxycaproic acid (3HC), and 3-6 mol % 3-hydroxydecanoic acid (3HD). The first-order degradation rate constants (k(1)) for the octanoate-derived PHA (designated P(3HO)) in the five species were in a similar range between 0.060 and 0.088 h(-1). This may indicate the similar specificities of the five intracellular depolymerases. In addition, the similar k(1) among the different species may correlate with the high degree of amino acid sequence identities (over 85%) among the intracellular PHA depolymerase phaZ genes. Six other chemically different types of PHA were accumulated in P. putida from n-nonanoic acid, n-decanoic acid, 5-phenyvaleric acid, or 11-phenoxyundecanoic acid as a single or a mixed carbon source. The calculated k(1) values were characteristic to each PHA, reflecting their chemical structures. In comparison with P(3HO), an increase in the levels of the two minor monomers 3HC and 3HD as in P(21 mol % 3HC-co-56 mol % 3HO-co-23 mol % 3HD) significantly slowed the rate of intracellular degradation. From the comparison of k(1) values, it is suggested that the P. putida intracellular depolymerase is most active against P(3HO).
ESTHER : Choi_2003_Biomacromolecules_4_424
PubMedSearch : Choi_2003_Biomacromolecules_4_424
PubMedID: 12625741

Title : The genome sequence of Yaba-like disease virus, a yatapoxvirus -
Author(s) : Lee HJ , Essani K , Smith GL
Ref : Virology , 281 :170 , 2001
PubMedID: 11277691
Gene_locus related to this paper: yabdi-13L

Title : Cloning and nucleotide sequence of the beta-galactosidase gene from Lactococcus lactis ssp. lactis ATCC7962. -
Author(s) : Lee JM , Chung DK , Park JH , Lee WK , Chang HC , Kim JH , Lee HJ
Ref : Biotechnol Lett , 19 :179 , 1997
Gene_locus related to this paper: lacla-Q9ZB16

Title : Cloning, sequencing and functional expression of an acetylcholinesterase gene from the yellow fever mosquito Aedes aegypti - Anthony_1995_FEBS.Lett_368_461
Author(s) : Anthony N , Rocheleau T , Mocelin G , Lee HJ , Ffrench-Constant R
Ref : FEBS Letters , 368 :461 , 1995
Abstract : A degenerate PCR strategy was used to isolate a fragment of the acetylcholinesterase gene (Ace) homolog from Aedes aegypti and screen for a cDNA clone containing the complete open reading frame of the gene. The predicted amino acid sequence of the Aedes gene shares 64% identity with Ace from Drosophila and 87% identity with the acetylcholinesterase gene from another mosquito species Anopheles stephensi. High levels of expression of the Aedes gene were achieved by infection of Sf21 cells with a recombinant baculovirus containing the Aedes Ace cDNA. The catalytic properties and sensitivity of the recombinant enzyme to insecticide inhibition are described and discussed in relation to the role of insensitive AChE in conferring resistance to organophosphorus and carbamate insecticides.
ESTHER : Anthony_1995_FEBS.Lett_368_461
PubMedSearch : Anthony_1995_FEBS.Lett_368_461
PubMedID: 7635199
Gene_locus related to this paper: aedae-ACHE

Title : Acetylcholine synthesis and release is enhanced by dibutyryl cyclic AMP in a neuronal cell line derived from mouse septum - Blusztajn_1992_J.Neurosci_12_793
Author(s) : Blusztajn JK , Venturini A , Jackson DA , Lee HJ , Wainer BH
Ref : Journal of Neuroscience , 12 :793 , 1992
Abstract : Cholinergic properties of the SN56.B5.G4 cell line derived from the fusion of neurons of the mouse postnatal day 21 septum and the murine neuroblastoma cell line N18TG2 were investigated and correlated with morphological differentiation. In basal serum-containing growth medium, few cells developed neurites. Neurite extension occurred in cells grown for 2 d with forskolin or dibutyryl cAMP (dbcAMP) but not with butyrate. In cells treated with these compounds, the activity of ChAT and ACh content were two- to threefold higher relative to controls. The cells synthesized ACh from choline taken up by the sodium-dependent high-affinity transport. Forskolin-, dbcAMP-, and butyrate-treated cells (but not the controls) were capable of spontaneous and depolarization-evoked ACh release. The results indicate that the morphological and the neurochemical aspects of SN56.B5.G4 cell differentiation are independently regulated.
ESTHER : Blusztajn_1992_J.Neurosci_12_793
PubMedSearch : Blusztajn_1992_J.Neurosci_12_793
PubMedID: 1312135

Title : Effects of various experimental manipulations on neostriatal acetylcholine and dopamine release - Lee_1991_Neurochem.Res_16_875
Author(s) : Lee HJ , Alcorn LM , Weiler MH
Ref : Neurochem Res , 16 :875 , 1991
Abstract : The release of endogenous acetylcholine and dopamine and the appearance of their metabolites, choline and dihydroxyphenylacetic acid (DOPAC), from neostriatal slices prepared from Fischer 344 rats was examined under various experimental conditions. There was a dose-dependent increase in the amount of neurotransmitter or metabolite as the medium potassium concentration was increased from 5 to 50 mM. Over an eight minute period in Krebs Ringer bicarbonate buffer containing 25 mM potassium, the rate of release of acetylcholine was 6 to 13 times greater than that of dopamine. The dopamine endogenous to the slice preparation appeared to have little effect on the release of endogenous acetylcholine since manipulations that significantly altered dopamine release (depletion with 6-hydroxydopamine or uptake inhibition with nomifensine) had minimal effects on the cholinergic neurons. In contrast, increasing the endogenous acetylcholine in the preparation by inhibiting acetylcholinesterase resulted in a 1.2 to 12 fold increase in dopamine release depending upon the incubation time and the potassium concentration. These studies indicate that within the neostriatal slices there is minimal influence of the endogenous dopamine on the cholinergic neurons, whereas the extracellular acetylcholine can influence dopamine release when its concentration is increased by inhibition of acetylcholinesterase.
ESTHER : Lee_1991_Neurochem.Res_16_875
PubMedSearch : Lee_1991_Neurochem.Res_16_875
PubMedID: 1787876

Title : Age-related differences in the effects of some muscarinic agents on acetylcholine release from rat neostriatal slices - Lee_1991_J.Pharmacol.Exp.Ther_258_496
Author(s) : Lee HJ , Cozzi NV , Weiler MH
Ref : Journal of Pharmacology & Experimental Therapeutics , 258 :496 , 1991
Abstract : The purpose of this study was to investigate whether the muscarinic modulation of neostriatal acetylcholine release changes with senescence. Neostriatal slices from Fischer 344 rats aged 3, 10 and 28 months were prepared and incubated in Krebs-Ringer bicarbonate buffer oxygenated with 95% O2/5% CO2. Acetylcholine release from slices of each age group was monitored in the presence or absence of muscarinic agents, and the release in the presence of the drug was compared to the release from slices of age-matched controls in the absence of drug. The muscarinic agonist, oxotremorine, and two muscarinic antagonists, atropine and pirenzepine, were tested for their effects on acetylcholine release. Pirenzepine is selective in its interaction with the M1 muscarinic receptor subtype; atropine and oxotremorine are nonselective in their actions. Of the three drugs tested, pirenzepine displayed a significant age-related difference in its effects on acetylcholine release. Whereas the effects of pirenzepine (50 microM) on acetylcholine release modulation in slices from the 3-month rats were negligible, the M1-selective antagonist increased the release of acetylcholine from slices of 10- and 28-month rats by another 42 and 192% (P less than .05), respectively. Atropine (1 microM) was also tested, and an increase in acetylcholine release by another 64, 104 and 218% (all P less than .05) was observed in slices from the 3-, 10- and 28-month rats, respectively. In the presence of oxotremorine (50 microM), acetylcholine release decreased in slices from the 3-month rats by 35% (P less than .1), but changed by only 7 and 15% in the 10- and 28-month slices, respectively.
ESTHER : Lee_1991_J.Pharmacol.Exp.Ther_258_496
PubMedSearch : Lee_1991_J.Pharmacol.Exp.Ther_258_496
PubMedID: 1865353