Zheng S

References (30)

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Deacylases-structure, function, and relationship to diseases - Wang_2024_FEBS.Lett_598_959
Author(s) : Wang S , Xing X , Ma J , Zheng S , Song Q , Zhang P
Ref : FEBS Letters , 598 :959 , 2024
Abstract : Reversible S-acylation plays a pivotal role in various biological processes, modulating protein functions such as subcellular localization, protein stability/activity, and protein-protein interactions. These modifications are mediated by acyltransferases and deacylases, among which the most abundant modification is S-palmitoylation. Growing evidence has shown that this rivalrous pair of modifications, occurring in a reversible cycle, is essential for various biological functions. Aberrations in this process have been associated with various diseases, including cancer, neurological disorders, and immune diseases. This underscores the importance of studying enzymes involved in acylation and deacylation to gain further insights into disease pathogenesis and provide novel strategies for disease treatment. In this Review, we summarize our current understanding of the structure and physiological function of deacylases, highlighting their pivotal roles in pathology. Our aim is to provide insights for further clinical applications.
ESTHER : Wang_2024_FEBS.Lett_598_959
PubMedSearch : Wang_2024_FEBS.Lett_598_959
PubMedID: 38644468

Title : PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer - Chen_2024_J.Transl.Med_22_249
Author(s) : Chen M , Zhang C , Li H , Zheng S , Li Y , Yuan M , Chen Y , Wu J , Sun Q
Ref : J Transl Med , 22 :249 , 2024
Abstract : BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.
ESTHER : Chen_2024_J.Transl.Med_22_249
PubMedSearch : Chen_2024_J.Transl.Med_22_249
PubMedID: 38454407

Title : Kj-mhpC Enzyme in Klebsiella jilinsis 2N3 Is Involved in the Degradation of Chlorimuron-Ethyl via De-Esterification - Zhai_2024_J.Agric.Food.Chem__
Author(s) : Zhai Q , Zheng S , Zhang C , Lu Z , Liang S , Li R , Zhang X , Pan H , Zhang H
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Microbial degradation is a highly efficient and reliable approach for mitigating the contamination of sulfonylurea herbicides, such as chlorimuron-ethyl, in soil and water. In this study, we aimed to assess whether Kj-mhpC plays a pivotal role in the degradation of chlorimuron-ethyl. Kj-mhpC enzyme purified via prokaryotic expression exhibited the highest catalytic activity for chlorimuron-ethyl at 35 degreesC and pH 7. Bioinformatic analysis and three-dimensional homologous modeling of Kj-mhpC were conducted. Additionally, the presence of Mg(+) and Cu(2+) ions partially inhibited but Pb(2+) ions completely inhibited the enzymatic activity of Kj-mhpC. LC/MS revealed that Kj-mhpC hydrolyzes the ester bond of chlorimuron-ethyl, resulting in the formation of 2-(4-chloro-6-methoxypyrimidine-2-amidoformamidesulfonyl) benzoic acid. Furthermore, the point mutation of serine at position 67 (Ser67) confirmed that it is the key amino acid at the active site for degrading chlorimuron-ethyl. This study enhanced the understanding of how chlorimuron-ethyl is degraded by microorganisms and provided a reference for bioremediation of the environment polluted with chlorimuron-ethyl.
ESTHER : Zhai_2024_J.Agric.Food.Chem__
PubMedSearch : Zhai_2024_J.Agric.Food.Chem__
PubMedID: 38417018
Gene_locus related to this paper: klep7-a6tb98

Title : Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys - Wang_2023_Mol.Ther.Nucleic.Acids_31_68
Author(s) : Wang J , Zheng W , Zheng S , Yuan Y , Wen W , Cui W , Xue L , Sun X , Shang H , Zhang H , Xiao RP , Gao S , Zhang X
Ref : Mol Ther Nucleic Acids , 31 :68 , 2023
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.
ESTHER : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedSearch : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedID: 36618267

Title : GR24-mediated enhancement of salt tolerance and roles of H(2)O(2) and Ca(2+) in regulating this enhancement in cucumber - Zhang_2022_J.Plant.Physiol_270_153640
Author(s) : Zhang XH , Ma C , Zhang L , Su M , Wang J , Zheng S , Zhang TG
Ref : J Plant Physiol , 270 :153640 , 2022
Abstract : This study investigated the regulation of the exogenous strigolactone (SL) analog GR24 in enhancing the salt tolerance and the effects of calcium ion (Ca(2+)) and hydrogen peroxide (H(2)O(2)) on GR24's regulation effects in cucumber. The seedlings were sprayed with (1) distilled water (CK), (2) NaCl, (3) GR24, then NaCl, (4) GR24, then H(2)O(2) scavenger, then NaCl, and (5) GR24, then Ca(2+) blocker, then NaCl. The second true leaf was selected for biochemical assays. Under the salt stress, the exogenous GR24 maintained the ion balance, increased the activity of antioxidant enzymes, reduced the membrane lipid peroxidation, and increased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), accompanied by a decrease in relative conductivity, an increase in the proline content, and elevated gene expression levels of antioxidant enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, calcium-dependent protein kinases (CDPKs), salt overly sensitive SOS1, CBL-interacting protein kinase 2 (CIPK2), and calcineurin B-like protein 3 (CBL3). Such protective effects triggered by GR24 were attenuated or almost abolished by ethylene glycol tetraacetic acid (EGTA), lanthanum chloride (LaCl3, Ca(2+) channel blocker), diphenyleneiodonium (DPI, NADPH oxidase inhibitor), and dimethylthiourea (DMTU, hydroxyl radical scavenger). Our data suggest that exogenous GR24 is highly effective in alleviating salt-induced damages via modulating antioxidant capabilities and improving ionic homeostasis and osmotic balance and that H(2)O(2) and Ca(2+) are required for GR24-mediated enhancement of salt tolerance.
ESTHER : Zhang_2022_J.Plant.Physiol_270_153640
PubMedSearch : Zhang_2022_J.Plant.Physiol_270_153640
PubMedID: 35168135

Title : A turn-on fluorescent probe based on ESIPT and AIEE mechanisms for the detection of butyrylcholinesterase activity in living cells and in non-alcoholic fatty liver of zebrafish - Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
Author(s) : Pei X , Fang Y , Gu H , Zheng S , Bin X , Wang F , He M , Lu S , Chen X
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 287 :122044 , 2022
Abstract : Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) are two important cholinesterase enzymes in human metabolism which are closely related to various diseases of the liver. BChE and AChE are difficult to be distinguished due to their similarity in biochemical properties. Therefore, developing BChE-specific probes with high sensitivity and low background reading is desirable for the relevant biological applications. Herein, we reported the design and synthesis of a fluorescent probe HBT-BChE for biological detection and imaging of BChE. The probe is triggered by BChE-mediated hydrolysis, releasing a fluorophore that holds AIEE and ESIPT properties with large Stokes shift (>100 nm), rendering the probe features of low background interference and high sensitivity. The probe can also distinguish BChE from AChE with a low detection limit of 7.540 x 10(-4) U/mL. Further in vitro studies have shown the ability of HBT-BChE to detect intracellular BChE activity, as well as to evaluate the efficiency of the BChE inhibitor. More importantly, the in vivo studies of imaging the BChE activity level in liver tissues using zebrafish as the model animal demonstrated the potential of HBT-BChE as a powerful tool for non-alcoholic fatty liver disease.
ESTHER : Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
PubMedSearch : Pei_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_287_122044
PubMedID: 36327810

Title : Presence of L1014F Knockdown-Resistance Mutation in Anopheles gambiae s.s. From So Tom and Prncipe - Zhang_2021_Front.Cell.Infect.Microbiol_11_633905
Author(s) : Zhang H , Li M , Tan R , Deng C , Huang B , Wu Z , Zheng S , Guo W , Tuo F , Yuan Y , Bandeira CA , Rompao DH , Xu Q , Song J , Wang Q
Ref : Front Cell Infect Microbiol , 11 :633905 , 2021
Abstract : Malaria, one of the most serious parasitic diseases, kills thousands of people every year, especially in Africa. Sao Tome and Prncipe are known to have stable transmission of malaria. Indoor residual spraying (IRS) of insecticides and long-lasting insecticidal nets (LLIN) are considered as an effective malaria control interventions in these places. The resistance status of Anopheles gambiae s.s. from Agua Grande, Caue, and Lemba of Sao Tome and Prncipe to insecticides, such as dichlorodiphenyltrichloroethane (DDT) (4.0%), deltamethrin (0.05%), permethrin (0.75%), fenitrothion (1.0%), and malathion (5.0%), were tested according to the WHO standard protocol. DNA extraction, species identification, as well as kdr and ace-1(R) genotyping were done with the surviving and dead mosquitoes post testing. They showed resistance to cypermethrin with mortality rates ranging from 89.06% to 89.66%. Mosquitoes collected from Agua Grande, Caue, and Lemba displayed resistance to DDT and fenitrothion with mortality rates higher than 90%. No other species were detected in these study localities other than Anopheles gambiae s.s. The frequency of L1014F was high in the three investigated sites, which was detected for the first time in Sao Tome and Prncipe. No ace(-1R) mutation was detected in all investigated sites. The high frequency of L1014F showed that kdr L1014F mutation might be related to insecticide resistance to Anopheles gambiae s.s. populations from Sao Tome and Prncipe. Insecticide resistance status is alarming and, therefore, future malaria vector management should be seriously considered by the government of Sao Tome and Prncipe.
ESTHER : Zhang_2021_Front.Cell.Infect.Microbiol_11_633905
PubMedSearch : Zhang_2021_Front.Cell.Infect.Microbiol_11_633905
PubMedID: 34307185

Title : Triglyceride-Mimetic Structure-Gated Prodrug Nanoparticles for Smart Cancer Therapy - Tian_2021_J.Med.Chem__
Author(s) : Tian C , Guo J , Miao Y , Zheng S , Sun B , Sun M , Ye Q , Liu W , Zhou S , Kamei KI , He Z , Sun J
Ref : Journal of Medicinal Chemistry , : , 2021
Abstract : Off-target drug release and insufficient drug delivery are the main obstacles for effective anticancer chemotherapy. Prodrug-based self-assembled nanoparticles bioactivated under tumor-specific conditions are one of the effective strategies to achieve on-demand drug release and effective tumor accumulation. Herein, stimuli-activable prodrugs are designed yielding smart tumor delivery by combination of the triglyceride-mimic (TG-mimetic) prodrug structure and disulfide bond. Surprisingly, these prodrugs can self-assemble into uniform nanoparticles (NPs) with a high drug loading (over 40%) and accumulate in tumor sites specifically. The super hydrophobic TG structure can act as a gate that senses lipase to selectively control over NP dissociation and affect the glutathione-triggered prodrug activation. In addition, the impacts of the double bonds in the prodrug NPs on parent drug release and the following cytotoxicity, pharmacokinetics, and antitumor efficiency are further demonstrated. Our findings highlight the promising potential of TG-mimetic structure-gated prodrug nanoparticles for tumor-specific drug delivery.
ESTHER : Tian_2021_J.Med.Chem__
PubMedSearch : Tian_2021_J.Med.Chem__
PubMedID: 34723524

Title : Biogenetic cantharidin is a promising leading compound to manage insecticide resistance of Mythimna separata (Lepidoptera: Noctuidae) - Li_2021_Pestic.Biochem.Physiol_172_104769
Author(s) : Li Y , Sun H , Yasoob H , Tian Z , Li R , Zheng S , Liu J , Zhang Y
Ref : Pestic Biochem Physiol , 172 :104769 , 2021
Abstract : Cantharidin (CTD) is a natural toxin with effective toxicity to lepidopteran pests. Nevertheless, little information is available on whether pests develop resistance to CTD. After being exposed to CTD (50 mg/L to 90 mg/L) or 10 generations, the resistance ratio of laboratory selected cantharidin-resistant Mythimna separata (Cantharidin-SEL) strain was only elevated 1.95-fold. Meanwhile, the developmental time for M. separata was prolonged (delayed1.65 in males and 1.84 days in females). The reported CTD target, the serine/threonine phosphatases (PSPs), have not been shown significant activity variation during the whole process of CTD-treatment. The activity of detoxification enzymes (cytochrome monooxygenase P450, glutathione-S-transferase (GST) and carboxylesterase) were affected by CTD selection, but this change was not mathematically significant. More importantly, no obvious cross-resistance with other commonly used insecticides was observed in the M. separata population treated with CTD for 10 generations (resistance ratios were all lower 2.5). Overall, M. separata is unlikely to produce target-site insensitivity resistance, metabolic resistance to CTD. Meanwhile, cantharidin-SEL is not prone to develop cross-resistance with other insecticides. These results indicate that CTD is a promising biogenetic lead compound which can be applied in the resistance management on M. separata.
ESTHER : Li_2021_Pestic.Biochem.Physiol_172_104769
PubMedSearch : Li_2021_Pestic.Biochem.Physiol_172_104769
PubMedID: 33518040

Title : Identification of key residues of carboxylesterase PxEst-6 involved in pyrethroid metabolism in Plutella xylostella (L.) - Li_2020_J.Hazard.Mater_407_124612
Author(s) : Li Y , Sun H , Tian Z , Ye X , Li R , Li X , Zheng S , Liu J , Zhang Y
Ref : J Hazard Mater , 407 :124612 , 2020
Abstract : The long-term and excessive use of insecticides has led to severe environmental problems and the evolution of insecticide resistance in insects. Carboxylesterases (CarEs) are important detoxification enzymes conferring insecticide resistance on insects. Herein, the detoxification process of Plutella xylostella (L.) carboxylesterase 6 (PxEst-6), one representative P. xylostella carboxylesterase, is investigated with cypermethrin, bifenthrin, cyfluthrin and lambda-cyhalothrin. RT-qPCR shows that PxEst-6 is highly expressed in the midgut and cuticles of the third instar larvae. Exposure to pyrethroid insecticides resulted in PxEst-6 up-regulation in a short time. Metabolic assays indicate that PxEst-6 has the capacity to metabolize these pyrethroid insecticides. The combination of molecular docking, binding mode analyses and alanine mutations demonstrated that His451, Lys458 and Gln431 were key residues of PxEst-6 for metabolizing pyrethroids and the acetate groups derived from pyrethroids were key sites for being metabolized by PxEst-6. H451- and K458-derived hydrogen bond (H-bond) interactions with the pyrethroid acetate groups and the polar interactions with the pyrethroid acetate group provided by the Q431 sidechain were crucial to the pyrethroids' metabolism by PxEst-6. Our study contributes to revealing the reasons for pyrethroid resistance in P. xylostella, and provides a fundamental basis for the development of novel pyrethroid insecticides.
ESTHER : Li_2020_J.Hazard.Mater_407_124612
PubMedSearch : Li_2020_J.Hazard.Mater_407_124612
PubMedID: 33338816
Gene_locus related to this paper: pluxy-f1c4b8

Title : Synthesis and biological evaluation of calycanthaceous alkaloid analogs - Zheng_2019_Bioorg.Med.Chem__115088
Author(s) : Zheng S , Zhu R , Zhou X , Chen L , Bai H , Zhang J
Ref : Bioorganic & Medicinal Chemistry , :115088 , 2019
Abstract : Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81microgmL(-1), respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63microgmL(-1). Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1ngmL(-1), respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4A. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
ESTHER : Zheng_2019_Bioorg.Med.Chem__115088
PubMedSearch : Zheng_2019_Bioorg.Med.Chem__115088
PubMedID: 31521458

Title : Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury - Niu_2018_Mol.Med.Rep_18_4516
Author(s) : Niu X , Zheng S , Liu H , Li S
Ref : Mol Med Rep , 18 :4516 , 2018
Abstract : The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a nonproteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead, cadmium, and exerciseinduced oxidative stress. Astrocytes and neuron cells were cocultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factoralpha, interleukin6, caspase3, p53, Bcell lymphoma 2 and Bcl2associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.
ESTHER : Niu_2018_Mol.Med.Rep_18_4516
PubMedSearch : Niu_2018_Mol.Med.Rep_18_4516
PubMedID: 30221665

Title : Kinetic resolution of sec-alcohols catalysed by Candida antarctica lipase B displaying Pichia pastoris whole-cell biocatalyst - Zhang_2018_Enzyme.Microb.Technol_110_8
Author(s) : Zhang K , Pan Z , Diao Z , Liang S , Han S , Zheng S , Lin Y
Ref : Enzyme Microb Technol , 110 :8 , 2018
Abstract : Kinetic resolution of sec-alcohols is a green process with biocatalyst. Candida antarctica lipase B (CALB) displayed on Pichia pastoris cell-surface (Pp-CALB) was characterized in kinetic resolution of sec-alcohols with different structures. The reaction parameters including acyl donors, molar ratio of substrates, solvents and temperatures were examined with 2-octanol as model substrate. 47.4% molar conversion of 2-octanol and 99.7% eep were obtained after a 5h reaction with Pp-CALB, and 90% of its original activity still remained after being reused for 10 cycles. Pp-CALB was then used to several sec-alcohols and it showed great enzymatic activity and enantioselectivity to all tested sec-alcohols, more than 93.1% of eep. The enantioselective characteristics of Pp-CALB catalysed sec-alcohols with different structures were compared with Novozyme 435 which was almost the same. Solvent free system as one way of green chemistry was applied to Pp-CALB and Pp-CALB showed great catalytic activity and enantioselectivity. Pp-CALB was potential biocatalyst of high enzymatic activity and enantioselectivity using in resolution of sec-alcohols.
ESTHER : Zhang_2018_Enzyme.Microb.Technol_110_8
PubMedSearch : Zhang_2018_Enzyme.Microb.Technol_110_8
PubMedID: 29310860

Title : Intoxication and biochemical responses of freshwater snail Bellamya aeruginosa to ethylbenzene - Zheng_2017_Environ.Sci.Pollut.Res.Int_24_189
Author(s) : Zheng S , Zhou Q
Ref : Environ Sci Pollut Res Int , 24 :189 , 2017
Abstract : No acute toxic data of ethylbenzene on gastropod is available in literature. In the present study, the acute toxicity of ethylbenzene was assessed on a freshwater snail Bellamya aeruginosa, which was exposed to ethylbenzene concentration from 1 to 100 mg/L for 96 h. No mortality occurred, but a manifestation of intoxication (distress syndrome) was observed in part of exposed snails, and meanwhile, another part was moved normally. The distress syndrome showed clear dose- and time-dependent effects, and the 96-h EC50 value for distress syndrome was 13.3 mg/L in snail. The biochemical responses induced by ethylbenzene to the snail, including acetylcholinesterase (AChE) in the whole body and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferases (GST), and reduced glutathione (GSH) in the hepatopancreas, were evaluated both for distressed snail and moved snail. The AChE activity of distressed snail was all inhibited more than 45 %, and the inhibition of AChE activity in the moved snail was all less than 30 % and more than 20 %, demonstrating that ethylbenzene exerted nervous toxicity to both distressed snail and moved snail. Meanwhile, the difference for AChE activity between the two different response snails was significant. Among the antioxidant biomarkers (SOD, CAT, GST, and GSH), only GST displayed significant difference between the distressed snail and moved snail. However, the activities of enzymes (SOD, CAT, and GST) in the moved snail were greater than those in the distressed snail, no matter significantly or insignificantly, which indicated that the ability of antioxidant defense in the distressed snail was weaker than that in the moved snail. The findings here reported manifest that ethylbenzene exerted nervous toxicity to snail, and the snail with intoxication response (distress syndrome) presented larger inhibition on AChE activity and weaker antioxidant ability in comparison with the moved snail.
ESTHER : Zheng_2017_Environ.Sci.Pollut.Res.Int_24_189
PubMedSearch : Zheng_2017_Environ.Sci.Pollut.Res.Int_24_189
PubMedID: 27709428

Title : High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers - Yu_2016_Oncotarget_7_75279
Author(s) : Yu J , Li X , Zhong C , Li D , Zhai X , Hu W , Guo C , Yuan Y , Zheng S
Ref : Oncotarget , 7 :75279 , 2016
Abstract : Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integratingproteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa. Meanwhile, Affymetrix U133plus2.0 microarrays were used to perform gene microarray analysis. Verification experiments included immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay (ELISA) of selected proteins. Overall, 5469 differentially expressed proteins were detected with iTRAQ-MS from 24 matched CRC and adjacent normal tissues. And gene microarray identified 39859 differential genes from 52 patients. Of these, 3083 differential proteins had corresponding differentially expressed genes, with 245 proteins and their genes showed >1.5-fold change in expression level. Gene ontology enrichment analysis revealed that up-regulated proteins were more involved in cell adhesion and motion than down-regulated proteins. In addition, up-regulated proteins were more likely to be located in nucleus and vesicles. Further verification experiments with IHC confirmed differential expression levels of 5 proteins (S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1) between CRC and normal tissues. Besides, western blot showed a stepwise increase of annexin A3 abundance in normal colorectal mucosa, adenoma and CRC tissues. ELISAresults revealed significantly higher serum levels of S100 calcium-binding protein A9 and annexin A3 in CRC patients than healthy controls, validating diagnostic value of these proteins. Cell experiments showed that inhibition of annexin A3 could suppress CRC cell proliferation and aggressiveness. S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1 were probably potential biomarkers of colorectal cancer. Annexin A3 was a potentially valuable therapeutic target of CRC.
ESTHER : Yu_2016_Oncotarget_7_75279
PubMedSearch : Yu_2016_Oncotarget_7_75279
PubMedID: 27661117

Title : Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1\; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male - Li_2014_Gene_547_43
Author(s) : Li L , Chen H , Yin C , Yang C , Wang B , Zheng S , Zhang J , Fan W
Ref : Gene , 547 :43 , 2014
Abstract : It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in the azoospermic male; however, the exact genetic damages are currently unknown for more than 40% of azoospermia. To elucidate the causative gene defects, we used the next generation sequencing (NGS) to map the breakpoints of a chromosome insertion from an azoospermic male who carries a balanced, maternally inherited karyotype 46, XY, inv ins (18,7) (q22.1; q36.2q21.11). The analysis revealed that the breakage in chromosome 7 disrupts two genes, dipeptidyl aminopeptidase-like protein 6 (DPP6) and contactin-associated protein-like 2 (CACNA2D1), the former participates in regulation of voltage-gated potassium channels, and the latter is one of the components in voltage-gated calcium channels. The deletion and duplication were not identified equal or beyond 100 kb, but 4 homologous DNA elements were verified proximal to the breakpoints. One of the proband's sisters inherited the same aberrant karyotype and experienced recurrent miscarriages and consecutive fetus death, while in contrast, another sister with a normal karyotype experienced normal labor and gave birth to healthy babies. The insertional translocation is confirmed with FISH and the Y-chromosome microdeletions were excluded by genetic testing. This is the first report describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1 to azoospermia.
ESTHER : Li_2014_Gene_547_43
PubMedSearch : Li_2014_Gene_547_43
PubMedID: 24937803

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Genome sequence of Corynebacterium glutamicum ATCC 14067, which provides insight into amino acid biosynthesis in coryneform bacteria - Lv_2012_J.Bacteriol_194_742
Author(s) : Lv Y , Liao J , Wu Z , Han S , Lin Y , Zheng S
Ref : Journal of Bacteriology , 194 :742 , 2012
Abstract : We report the genome sequence of Corynebacterium glutamicum ATCC 14067 (once named Brevibacterium flavum), which is useful for taxonomy research and further molecular breeding in amino acid production. Preliminary comparison with those of the reported coryneform strains revealed some notable differences that might be related to the difficulties in molecular manipulation.
ESTHER : Lv_2012_J.Bacteriol_194_742
PubMedSearch : Lv_2012_J.Bacteriol_194_742
PubMedID: 22247536
Gene_locus related to this paper: corgl-Cgl1133 , corgl-Cgl2249 , corgl-CGL2393 , corgl-q8nlr5 , corgl-q8nlz1 , corgt-g6wsn6

Title : Genome sequence of Corynebacterium glutamicum S9114, a strain for industrial production of glutamate - Lv_2011_J.Bacteriol_193_6096
Author(s) : Lv Y , Wu Z , Han S , Lin Y , Zheng S
Ref : Journal of Bacteriology , 193 :6096 , 2011
Abstract : Here we report the genome sequence of Corynebacterium glutamicum S9114, an industrial producer widely used in production of glutamate in China. Preliminary comparison with the sequences of the Corynebacterium glutamicum strains ATCC 13032 and R revealed some notable mutagenesis that might be related to the high yield of glutamate.
ESTHER : Lv_2011_J.Bacteriol_193_6096
PubMedSearch : Lv_2011_J.Bacteriol_193_6096
PubMedID: 21994927
Gene_locus related to this paper: corgl-Cgl1133 , corgl-Cgl2249 , corgl-CGL2393 , corgl-q8nlr5 , corgt-g6wsn6

Title : [Expression of Candida antarctica lipase B on yeast surface and synthesis of ethyl hexanoate catalyzed by CALB] - Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
Author(s) : Pan Z , Han S , Lin Y , Zheng S
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :673 , 2008
Abstract : Short-chain esters play a significant role in the food industry as flavor and aroma constituents. Candida antarctica lipase B (CALB) is one of the most effective catalysts for organic synthesis. We constructed a CALB-displaying yeast whole-cell biocatalyst and applied it to esterification from caproic acid and ethanol. CALB was fused with the alpha-agglutinin C-terminal and the signal peptide of Glucoamylase in pICAS, a yeast surface display vector, to construct plasmid pICAS-CALB. An extremely Asn-rich linker, named celAL was inserted in the Xho I of pICAS-CALB to construct plasmid pICAS-celAL-CALB. The fused gene was under the control of GAPDH promoter. After incubated at 30 degrees C for 96 h the lipase hydrolytic activity of the yeast whole cells reached a plateau, 26.26 u/(g x dry cell). In nonaqeous media, the yield of 98.0% ethyl hexanoate was obtained after 24 h esterification from caproic acid and ethanol (the molar ratio of caproic acid : ethanol = 1 : 1.25) using lyophilized CALB displaying yeast whole cells.
ESTHER : Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
PubMedSearch : Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
PubMedID: 18616181

Title : Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B - He_2007_Bioorg.Med.Chem_15_1394
Author(s) : He XC , Feng S , Wang ZF , Shi Y , Zheng S , Xia Y , Jiang H , Tang XC , Bai D
Ref : Bioorganic & Medicinal Chemistry , 15 :1394 , 2007
Abstract : Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives of HupB was enhanced about 2-3 orders of magnitude as compared with the parental HupB. Among bis-HupB derivatives, 12h exhibited the most potent in the AChE inhibition and has been evaluated for its pharmacological actions in vivo on ChE inhibition, cognitive enhancement, and neuroprotection. The docking study on the bis-HupB derivatives 12 series with TcAChE has demonstrated that the ligands bound to the dual-site of the enzyme in different level.
ESTHER : He_2007_Bioorg.Med.Chem_15_1394
PubMedSearch : He_2007_Bioorg.Med.Chem_15_1394
PubMedID: 17126020

Title : Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase - Sheng_2006_Eur.J.Pharmacol_543_116
Author(s) : Sheng L , Qian Z , Zheng S , Xi L
Ref : European Journal of Pharmacology , 543 :116 , 2006
Abstract : The hypolipidemic mechanism of crocin, an active ingredient in Gardenia jasminoides Ellis and Crocus sativus L, was examined in rats. In diet-induced hyperlipidemic rats, a 10-day treatment with crocin significantly reduced serum triglyceride, total cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol level in the daily dose range of 25 to 100 mg/kg. Results of the modified fat-loading method indicated that crocin inhibited the absorption of fat and cholesterol and this inhibition is closely related to the hydrolysis of fat. In addition, the modified fat-balance method demonstrated that crocin increased the fecal excretion of fat and cholesterol in rats, but had no influence on the elimination of bile acids. The results of the in situ loop method and enzyme assay indicated that crocin could not directly block the absorption of cholesterol from rat jejunum but could selectively inhibit the activity of pancreatic lipase as a competitive inhibitor. These findings suggest that crocin yielded its hypolipidemic effect by inhibiting pancreatic lipase, leading to the malabsorption of fat and cholesterol.
ESTHER : Sheng_2006_Eur.J.Pharmacol_543_116
PubMedSearch : Sheng_2006_Eur.J.Pharmacol_543_116
PubMedID: 16828739

Title : Adulticidal Activity of Five Essential Oils against Culex pipiens quinquefasciatus - Yang_2005_J.Pestic.Sci_30_84
Author(s) : Yang P , Ma Y , Zheng S
Ref : Journal of Pesticide Science , 30 :84 , 2005
Abstract : The aim of this study is to observe the adulticidal activity of five essential oils against the mosquito Culex pipiens quinquefasciatus. Fumigating adulticidal activity was investigated by airtight fumigation in conical flasks. The result showed that the toxic effect of the five essential oils varied with the period of fumigation. Rutaceae oil was the most toxic of the five. Carvacryl oil had the shortest adulticidal time (6.087 min). The chemical components of rutaceae oil were analyzed by GC/MS. The major components were alpha-citral (33.50%) and citral (35.77%). Citral showed marked adulticidal activity in a short-term fumigation. All five essential oils had considerable adulticidal effects on Cx. pipiens quinquefasciatus.
ESTHER : Yang_2005_J.Pestic.Sci_30_84
PubMedSearch : Yang_2005_J.Pestic.Sci_30_84

Title : Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors - Feng_2005_J.Med.Chem_48_655
Author(s) : Feng S , Wang Z , He X , Zheng S , Xia Y , Jiang H , Tang X , Bai D
Ref : Journal of Medicinal Chemistry , 48 :655 , 2005
Abstract : By targeting dual active sites of AChE, a series of bis-huperzine B analogues with various lengths of the tether were designed, synthesized, and tested for their inhibition and selectivity. The most potent bis-huperzine B (5g) exhibited 3900-fold increase in AChE inhibition and 930-fold greater in selectivity for AChE vs BuChE than its parent huperzine B.
ESTHER : Feng_2005_J.Med.Chem_48_655
PubMedSearch : Feng_2005_J.Med.Chem_48_655
PubMedID: 15689148

Title : Secretion, purification, and characterization of a recombinant Aspergillus oryzae tannase in Pichia pastoris - Zhong_2004_Protein.Expr.Purif_36_165
Author(s) : Zhong X , Peng L , Zheng S , Sun Z , Ren Y , Dong M , Xu A
Ref : Protein Expr Purif , 36 :165 , 2004
Abstract : Tannase (tannin acyl hydrolase) is an industrially important enzyme produced by a large number of fungi, which hydrolyzes the ester and depside bonds of gallotannins and gallic acid esters. In the present work, a tannase from Aspergillus oryzae has been cloned and expressed in Pichia pastoris. The catalytic activity of the recombinant enzyme was assayed. A secretory form of enzyme was made with the aid of Saccharomyces cerevisiae alpha-factor, and a simple procedure purification protocol yielded tannase in pure form. The productivity of secreted tannase achieved 7000 IU/L by fed-batch culture. Recombinant tannase had a molecular mass of 90 kDa, which consisted of two kinds of subunits linked by a disulfide bond(s). Our study is the first report on the heterologous expression of tannase suggesting that the P. pastoris system represents an attractive means of generating large quantities of tannase for both research and industrial purpose.
ESTHER : Zhong_2004_Protein.Expr.Purif_36_165
PubMedSearch : Zhong_2004_Protein.Expr.Purif_36_165
PubMedID: 15249037
Gene_locus related to this paper: aspor-tan

Title : Identification and characterization of a juvenile hormone (JH) response region in the JH esterase gene from the spruce budworm, Choristoneura fumiferana - Kethidi_2004_J.Biol.Chem_279_19634
Author(s) : Kethidi DR , Perera SC , Zheng S , Feng QL , Krell P , Retnakaran A , Palli SR
Ref : Journal of Biological Chemistry , 279 :19634 , 2004
Abstract : Using a differential display of mRNA technique we discovered that the juvenile hormone (JH) esterase gene (Cfjhe) from Choristoneura fumiferana is directly induced by juvenile hormone I (JH I), and the JH I induction is suppressed by 20-hydroxyecdysone (20E). To study the mechanism of action of these two hormones in the regulation of expression of this gene, we cloned the 1270-bp promoter region of the Cfjhe gene and identified a 30-bp region that is located between -604 and -574 and is sufficient to support both JH I induction and 20E suppression. This 30-bp region contains two conserved hormone response element half-sites separated by a 4-nucleotide spacer similar to the direct repeat 4 element and is designated as a putative juvenile hormone response element (JHRE). In CF-203 cells, a luciferase reporter placed under the control of JHRE and a minimal promoter was induced by JH I in a dose- and time-dependent manner. Moreover, 20E suppressed this JH I-induced luciferase activity in a dose- and time-dependent manner. Nuclear proteins isolated from JH I-treated CF-203 cells bound to JHRE and the binding was competed by a 100-fold excess of the cold probe but not by 100-fold excess of double-stranded oligonucleotides of unrelated sequence. JH I induced/modified nuclear proteins prior to their binding to JHRE and 20E suppressed this JH I induction/modification. These results suggest that the 30-bp JHRE identified in the Cfjhe gene promoter is sufficient to support JH induction and 20E suppression of the Cfjhe gene.
ESTHER : Kethidi_2004_J.Biol.Chem_279_19634
PubMedSearch : Kethidi_2004_J.Biol.Chem_279_19634
PubMedID: 14990570

Title : CYP1A1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma: study of population from a high- incidence area in north China - Wang_2003_World.J.Gastroenterol_9_1394
Author(s) : Wang LD , Zheng S , Liu B , Zhou JX , Li YJ , Li JX
Ref : World J Gastroenterol , 9 :1394 , 2003
Abstract : AIM: To characterize cytochrome P4501A1 (CYP1A1), glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEH) polymorphisms in Chinese esophageal cancer patients. METHODS: Multiplex polymerase chain reaction (PCR) and PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect polymorphism changes of CYP, GSTs and mEH on esophageal cancerous and precancerous lesions as well as in case control group. All the examination samples were obtained from Linzhou (formerly Linxian), Henan Province, the highest incidence area for esophageal cancer. RESULTS: The frequency of CYP1A1 3' polymorphism in case control group (26/38, 68 %) was significantly higher than in esophageal squamous cell carcinoma group (ESCC) (29/62, 47 %) (P<0.05). A significant difference in the incidence of mEH slow allele variant was observed between case control group (15/38, 39 %) and esophageal dysplasia group (22/32, 69 %) or ESCC group (39/62, 63 %) (P<0.05). However, no significant difference was observed among different groups in the polymorphisms of CYP1A1 exon 7, GSTM1, GSTT1, GSTP1 and mEH fast allele. CONCLUSION: The present results suggest that CYP1A1 3' polymorphism may be one of the promising protective factors and its wild gene type may be an indicator for higher susceptibility to esophageal cancer. mEH slow allele variant, associated with the progression of esophageal precancerous lesions, may contribute to the high susceptibility to esophageal carcinoma.
ESTHER : Wang_2003_World.J.Gastroenterol_9_1394
PubMedSearch : Wang_2003_World.J.Gastroenterol_9_1394
PubMedID: 12854128

Title : Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis - Kirby_2002_J.Biol.Chem_277_4104
Author(s) : Kirby RJ , Zheng S , Tso P , Howles PN , Hui DY
Ref : Journal of Biological Chemistry , 277 :4104 , 2002
Abstract : Bile salt-stimulated carboxyl ester lipase (CEL), also called cholesterol esterase, is one of the major proteins secreted by the pancreas. The physiological role of CEL was originally thought to be its mediation of dietary cholesterol absorption. However, recent studies showed no difference between wild type and CEL knockout mice in the total amount of cholesterol absorbed in a single meal. The current study tests the hypothesis that CEL in the intestinal lumen may influence the type of lipoproteins produced. A lipid emulsion containing 4 mm phospholipid, 13.33 mm [(3)H]triolein, and 2.6 mm [(14)C]cholesterol in 19 mm taurocholate was infused into the duodenum of lymph fistula CEL(+/+) and CEL(-/-) mice at a rate of 0.3 ml/h. Results showed no difference between CEL(+/+) and CEL(-/-) mice in the rate of cholesterol and triglyceride transport from the intestinal lumen to the lymph. However, CEL(-/-) mice produced predominantly smaller lipoproteins, whereas the CEL(+/+) mice produced primarily large chylomicrons and very low density lipoprotein. The proximal intestine of CEL(-/-) mice was also found to possess significantly less ceramide hydrolytic activity than that present in CEL(+/+) mice. By using Caco2 cells grown on Transwell membranes as a model, sphingomyelinase treatment inhibited the secretion of larger chylomicron-like lipoproteins without affecting total cholesterol secretion. In contrast, the addition of CEL to the apical medium increased the amount of large lipoproteins produced and alleviated the inhibition induced by sphingomyelinase. Taken together, this study identified a novel and physiologically significant role for CEL, namely the promotion of large chylomicron production in the intestine. The mechanism appears to be mediated through CEL hydrolysis of ceramide generated during the lipid absorption process.
ESTHER : Kirby_2002_J.Biol.Chem_277_4104
PubMedSearch : Kirby_2002_J.Biol.Chem_277_4104
PubMedID: 11733511

Title : Wnt-1 inhibits nerve growth factor-induced differentiation of PC12 cells by preventing the induction of some but not all late-response genes - Chou_2000_Brain.Res.Mol.Brain.Res_77_232
Author(s) : Chou AH , Zheng S , Itsukaichi T , Howard BD
Ref : Brain Research Mol Brain Res , 77 :232 , 2000
Abstract : The vertebrate Wnt-1 proto-oncogene is expressed transiently in embryonic brain and functions in the development of the central nervous system and neural crest. The role of Wnt-1 in neural crest development appears to be to increase the number of certain progenitor cells by preventing their premature differentiation. To study the mechanism by which this transient Wnt-1 expression inhibits differentiation we have constructed PC12 pheochromocytoma cells in which Wnt-1 expression levels were controlled by use of a tetracycline-responsive transactivator. Induction of Wnt-1 expression by tetracycline withdrawal was followed by activation of the Wnt-1 signalling pathway as shown by activation of the Lef-1/Tcf transcription factor. Wnt-1 expression by these cells resulted in reversible inhibition of NGF-induced neurite outgrowth, but it did not adversely affect the maintenance of previously formed NGF-induced neurites. Wnt-1 expression also partially blocked the ability of NGF to decrease the rate of cell multiplication. Wnt-1 decreased the NGF-induced expression of the late-response gene SCG10 but not of the immediate early genes, fos, Nur77 and UPAR (urokinase-type plasminogen activator receptor) nor of the late-response genes GAP-43 and collagenase. The Wnt-1 expressing PC12 cells multiplied at a greater rate when they expressed Wnt-1 than they did in the absence of Wnt-1 expression, a result that is consistent with the proposal that Wnt-1 may also act as a mitogen.
ESTHER : Chou_2000_Brain.Res.Mol.Brain.Res_77_232
PubMedSearch : Chou_2000_Brain.Res.Mol.Brain.Res_77_232
PubMedID: 10837918