Inoue H

References (17)

Title : Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models - Matsukawa_2023_JCI.Insight_8__e161282
Author(s) : Matsukawa T , Yagi T , Uchida T , Sakai M , Mitsushima M , Naganuma T , Yano H , Inaba Y , Inoue H , Yanagida K , Uematsu M , Nakao K , Nakao H , Aiba A , Nagashima Y , Kubota T , Kubota N , Izumida Y , Yahagi N , Unoki-Kubota H , Kaburagi Y , Asahara SI , Kido Y , Shindou H , Itoh M , Ogawa Y , Minami S , Terauchi Y , Tobe K , Ueki K , Kasuga M , Matsumoto M
Ref : JCI Insight , 8 : , 2023
Abstract : Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
ESTHER : Matsukawa_2023_JCI.Insight_8__e161282
PubMedSearch : Matsukawa_2023_JCI.Insight_8__e161282
PubMedID: 37681411
Gene_locus related to this paper: human-FASN , mouse-FASN

Title : Organophosphate agent action at the fatty acid amide hydrolase enhancing anandamide-induced apoptosis in NG108-15 cells - Terajima_2023_J.Toxicol.Sci_48_421
Author(s) : Terajima T , Inoue H , Shimomura K , Iwasaki F , Sasaki A , Ito Y , Kamijima M , Tomizawa M
Ref : Journal of Toxicological Sciences , 48 :421 , 2023
Abstract : Organophosphate (OP) agents are continuously utilized in large amount throughout the globe for crop protection and public health, thereby creating a potential concern on human health. OP agent as an anticholinesterase also acts on the endocannabinoid (EC)-hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), to reveal unexpected adverse effects including ADHD-like behaviors in adolescent male rats. The present investigation examines a hypothesis that OP compound inhibiting the EC-hydrolase(s) dysregulates the EC-signaling system, triggering apoptosis in neuronal cells. Ethyl octylphosphonofluoridate (EOPF), as an OP probe, preferably acts on FAAH over MAGL in intact NG108-15 cells. Anandamide (AEA), an endogenous FAAH substrate, is cytotoxic in a concentration-dependent manner, although 2-arachidonoylglycerol, an endogenous MAGL substrate, gives no effect in the concentrations examined here. EOPF pretreatment markedly enhances AEA-induced cytotoxicity. Interestingly, the cannabinoid receptor blocker AM251 diminishes AEA-induced cell death, whereas AM251 does not prevent the cell death in the presence of EOPF. The consistent results are displayed in apoptosis markers evaluation (caspases and mitochondrial membrane potential). Accordingly, FAAH inhibition by EOPF suppresses AEA-metabolism, and accumulated excess AEA overstimulates both the cannabinoid receptor- and mitochondria-mediated apoptotic pathways.
ESTHER : Terajima_2023_J.Toxicol.Sci_48_421
PubMedSearch : Terajima_2023_J.Toxicol.Sci_48_421
PubMedID: 37394655

Title : Acetylation of amines and alcohols catalyzed by acetylcholinesterase from Pseudomonas aeruginosa PAO1 - Inoue_2023_Enzyme.Microb.Technol_165_110208
Author(s) : Inoue H , Tachibana T , Bito T , Arima J
Ref : Enzyme Microb Technol , 165 :110208 , 2023
Abstract : Acetylcholinesterase (AChE) from Pseudomonas aeruginosa PAO1 has a catalytic Ser residue in its active site. In this study, we examined the aminolysis and alcoholysis reactions of AChE that occurred alongside its hydrolysis reaction. The recombinant AChE recognized ethyl acetate as a substrate. Therefore, we evaluated acetylation of the amine and hydroxyl group by AChE, using acetylcholine and ethyl acetate as the acetyl donor. AChE recognized diaminoalkanes with 4- to 12-carbon chains and aminoalcohols with 4- to 8-carbon chains as acetyl acceptors, resulting in their acetylated products. In the acetylation of 1,6-diaminohexane, AChE preferentially used ethyl acetate as the acetyl donor above pH 8.0 and the efficiency increased with increasing pH. In contrast, the acetylation of 6-amino-1-hexanol was efficient with acetylcholine as the acetyl donor in the pH range of 4-10. In addition, acetylated 6-amino-1-hexanol was decomposed by AChE. The kinetic study indicated that the acetyl donor and acceptor are competitively recognized by AChE as substrates.
ESTHER : Inoue_2023_Enzyme.Microb.Technol_165_110208
PubMedSearch : Inoue_2023_Enzyme.Microb.Technol_165_110208
PubMedID: 36753877

Title : Mechanism of central hypopnoea induced by organic phosphorus poisoning - Nomura_2020_Sci.Rep_10_15834
Author(s) : Nomura K , Narimatsu E , Inoue H , Kyan R , Sawamoto K , Uemura S , Kakizaki R , Harada K
Ref : Sci Rep , 10 :15834 , 2020
Abstract : Whether central apnoea or hypopnoea can be induced by organophosphorus poisoning remains unknown to date. By using the acute brainstem slice method and multi-electrode array system, we established a paraoxon (a typical acetylcholinesterase inhibitor) poisoning model to investigate the time-dependent changes in respiratory burst amplitudes of the pre-Botzinger complex (respiratory rhythm generator). We then determined whether pralidoxime or atropine, which are antidotes of paraoxon, could counteract the effects of paraoxon. Herein, we showed that paraoxon significantly decreased the respiratory burst amplitude of the pre-Botzinger complex (p < 0.05). Moreover, pralidoxime and atropine could suppress the decrease in amplitude by paraoxon (p < 0.05). Paraoxon directly impaired the pre-Botzinger complex, and the findings implied that this impairment caused central apnoea or hypopnoea. Pralidoxime and atropine could therapeutically attenuate the impairment. This study is the first to prove the usefulness of the multi-electrode array method for electrophysiological and toxicological studies in the mammalian brainstem.
ESTHER : Nomura_2020_Sci.Rep_10_15834
PubMedSearch : Nomura_2020_Sci.Rep_10_15834
PubMedID: 32985607

Title : Fluorescein diacetate (FDA) and its analogue as substrates for Pi-class glutathione S-transferase (GSTP1) and their biological application - Fujikawa_2018_Talanta_179_845
Author(s) : Fujikawa Y , Nampo T , Mori M , Kikkawa M , Inoue H
Ref : Talanta , 179 :845 , 2018
Abstract : Pi class glutathione S-transferase (GSTP1) is highly expressed in various cancerous cells and pre-neoplastic legions, where it is involved in apoptotic resistance or metabolism of several anti-tumour chemotherapeutics. Therefore, GSTP1 is a marker of malignant and pre-malignant cells and is a promising target for visualization and drug development. Here we demonstrate that fluorescein diacetate (FDA), a fluorescent probe used for vital staining, is a fluorescently activated by esterolytic activity of human GSTP1 (hGSTP1) selectively among various cytosolic GSTs. Fluorescence activation of FDA susceptible to GST inhibitors was observed in MCF7 cells exogenously overexpressing hGSTP1, but not in cells overexpressing hGSTA1 or hGSTM1. Inhibitor-sensitive fluorescence activation was also observed in several cancer cell lines endogenously expressing GSTP1, suggesting that GSTP1 is involved in FDA esterolysis in these cells. Among the FDA derivatives examined, FOMe-Ac, the acetyl ester of fluorescein O-methyl ether, was found to be a potential reporter for GSH-dependent GSTP1 activity as well as for carboxylesterase activity. Since GSTP1 is highly expressed in various types of cancer cells compared to their normal counterparts, improving the fluorogenic substrates to be more selective to the esterolysis activity of GSTP1 rather than carboxylesterases should lead to development of tools for detecting GSTP1-overexpressing cancer cells and investigating the biological functions of GSTP1.
ESTHER : Fujikawa_2018_Talanta_179_845
PubMedSearch : Fujikawa_2018_Talanta_179_845
PubMedID: 29310316

Title : Characterization of a feruloyl esterase B from Talaromyces cellulolyticus - Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
Author(s) : Watanabe M , Yoshida E , Fukada H , Inoue H , Tokura M , Ishikawa K
Ref : Biosci Biotechnol Biochem , 79 :1845 , 2015
Abstract : A feruloyl esterase catalyzes the hydrolysis of the 4-hydroxy-3-methoxycinnamoyl (feruloyl) group from esterified sugars in plant cell walls. Talaromyces cellulolyticus is a high cellulolytic-enzyme producing fungus. However, there is no report for feruloyl esterase activity of T. cellulolyticus. Analysis of the genome database of T. cellulolyticus identified a gene encoding a putative feruloyl esterase B. The recombinant enzyme was prepared using a T. cellulolyticus homologous expression system and characterized. The purified enzyme exhibited hydrolytic activity toward p-nitrophenyl acetate, p-nitrophenyl trans-ferulate, methyl ferulate, rice husk, and bagasse. HPLC assays showed that the enzyme released ferulic acid and p-coumaric acid from hydrothermal-treated rice husk and bagasse. Trichoderma sp. is well-known high cellulolytic-enzyme producing fungus useful for the lignocellulosic biomass saccharification. Interestingly, no feruloyl esterase has been reported from Trichoderma sp. The results show that this enzyme is expected to be industrially useful for biomass saccharification.
ESTHER : Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
PubMedSearch : Watanabe_2015_Biosci.Biotechnol.Biochem_79_1845
PubMedID: 26110915
Gene_locus related to this paper: talce-faeB

Title : Crystal structure of an acetylesterase from Talaromyces cellulolyticus and the importance of a disulfide bond near the active site - Watanabe_2015_FEBS.Lett_589_1200
Author(s) : Watanabe M , Fukada H , Inoue H , Ishikawa K
Ref : FEBS Letters , 589 :1200 , 2015
Abstract : Carbohydrate esterase catalyzes the de-O or de-N-acylation of substituted saccharides in plant cell walls and thus has great potential for industrial biomass saccharification. We recently identified the putative carbohydrate esterase family 3 (CE3) from Talaromyces cellulolyticus. Here, we prepared the recombinant catalytic domain of the enzyme and crystallized it. The crystal structure was determined to 1.5A resolution. From the structural analysis, it was elucidated that a n-octyl-beta-d-glucopyranoside bound to near the catalytic triad (Ser10, Asp179 and His182) and was buried in the active site cavity. Site-directed mutagenesis showed that the N-terminal disulfide bond located near the catalytic triad is involved in the activity and structural stability of the enzyme.
ESTHER : Watanabe_2015_FEBS.Lett_589_1200
PubMedSearch : Watanabe_2015_FEBS.Lett_589_1200
PubMedID: 25825334

Title : Sorafenib attenuates p21 in kidney cancer cells and augments cell death in combination with DNA-damaging chemotherapy - Inoue_2011_Cancer.Biol.Ther_12_827
Author(s) : Inoue H , Hwang SH , Wecksler AT , Hammock BD , Weiss RH
Ref : Cancer Biol Ther , 12 :827 , 2011
Abstract : There are few effective therapeutic options for metastatic renal cell carcinoma (RCC). Conventional chemotherapeutic agents are ineffective since these tumors are unusually resistant to DNA damage, likely due to an exuberant DNA repair response. Sorafenib, as one of the few available effective therapeutic options for metastatic RCC, has been shown to inhibit cell proliferation by inhibition of tyrosine kinases. We have recently shown that sorafenib inhibits soluble epoxide hydrolase, which catalyzes metabolism of the anti-inflammatory epoxyeicosatrienoic acids. Given previous work demonstrating the anti-apoptotic role of p21 in RCC as a potential mechanism for its drug resistance, we asked whether sorafenib signals through this pathway. We now show that sorafenib markedly decreases p21 levels in several RCC and hepatocellular carcinoma cells. Neither the MEK inhibitor PD98059 nor the sEH inhibitor t-AUCB, which represent known sorafenib-targeted signaling pathways, alter p21 levels, demonstrating that the p21 inhibitory effect of sorafenib is independent of these signaling cascades. In cells treated with doxorubicin to augment p21, sorafenib markedly decreases this protein, and the combinations of paclitaxel or doxorubicin with sorafenib show additive cytotoxicity as a function of the VHL status of the cells, suggesting that lower doses of each agent could be used in the clinical setting. In summary, we show a novel signaling pathway by which sorafenib exerts its salutary effects in RCC; future work will focus on the use of these drug combinations in the context of conventional therapeutics, and novel compounds and protocols targeting p21 in conjunction with sorafenib should be pursued.
ESTHER : Inoue_2011_Cancer.Biol.Ther_12_827
PubMedSearch : Inoue_2011_Cancer.Biol.Ther_12_827
PubMedID: 21878748

Title : Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models - Takeuchi_2009_J.Neurosci.Res_87_576
Author(s) : Takeuchi H , Yanagida T , Inden M , Takata K , Kitamura Y , Yamakawa K , Sawada H , Izumi Y , Yamamoto N , Kihara T , Uemura K , Inoue H , Taniguchi T , Akaike A , Takahashi R , Shimohama S
Ref : Journal of Neuroscience Research , 87 :576 , 2009
Abstract : Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra. Although the entire pathogenesis of PD is still unclear, both environmental and genetic factors contribute to neurodegeneration. Epidemiologic studies show that prevalence of PD is lower in smokers than in nonsmokers. Nicotine, a releaser of dopamine from DA neurons, is one of the candidates of antiparkinson agents in tobacco. To assess the protective effect of nicotine against rotenone-induced DA neuronal cell toxicity, we examined the neuroprotective effects of nicotine in rotenone-induced PD models in vivo and in vitro. We observed that simultaneous subcutaneous administration of nicotine inhibited both motor deficits and DA neuronal cell loss in the substantia nigra of rotenone-treated mice. Next, we analyzed the molecular mechanisms of DA neuroprotective effect of nicotine against rotenone-induced toxicity with primary DA neuronal culture. We found that DA neuroprotective effects of nicotine were inhibited by dihydro-beta-erythroidine (DHbetaE), alpha-bungarotoxin (alphaBuTx), and/or PI3K-Akt/PKB (protein serine/threonine kinase B) inhibitors, demonstrating that rotenone-toxicity on DA neurons are inhibited via activation of alpha4beta2 or alpha7 nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone mouse model may be useful for assessing candidate antiparkinson agents, and that nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons against degeneration.
ESTHER : Takeuchi_2009_J.Neurosci.Res_87_576
PubMedSearch : Takeuchi_2009_J.Neurosci.Res_87_576
PubMedID: 18803299

Title : In vitro stability and metabolism of salvinorin A in rat plasma - Tsujikawa_2009_Xenobiotica_39_391
Author(s) : Tsujikawa K , Kuwayama K , Miyaguchi H , Kanamori T , Iwata YT , Inoue H
Ref : Xenobiotica , 39 :391 , 2009
Abstract : Salvinorin A is the main active psychoactive ingredient in Salvia divinorum, a Mexican plant that has been widely available as a hallucinogen in recent years. The aims of this study were to investigate the stability of salvinorin A in rat plasma, esterases responsible for its degradation, and estimation of the degradation products. The apparent first-order rate constants of salvinorin A at 37 degrees C, 25 degrees C, and 4 degrees C were 3.8 x 10(-1), 1.1 x 10(-1), and < 6.0 x 10(-3) h(-1), respectively. Salvinorin A degradation was markedly inhibited by the addition of sodium fluoride, an esterase inhibitor. Moreover, phenylmethylsulfonyl fluoride (serine esterase inhibitor) and bis-p-nitrophenylphosphate (carboxylesterase inhibitor) also inhibited salvinorin A degradation. In contrast, little or no suppression of the degradation was seen with 5,5'-dithiobis-2-nitrobenzoic acid (arylesterase inhibitor),ethopropazine (butyrylcholinesterase inhibitor), and BW284c51 (acetylcholineseterase inhibitor). These findings indicated that carboxylesterase was mainly involved in the salvinorin A hydrolysis in rat plasma.4. The degradation products of salvinorin A estimated by liquid chromatography-mass spectrometry included the deacetylated form (salvinorin B) and the lactone-ring-open forms of salvinorin A and salvinorin B. This lactone-ring-opening reactions were involved in calcium-dependent lactonase.
ESTHER : Tsujikawa_2009_Xenobiotica_39_391
PubMedSearch : Tsujikawa_2009_Xenobiotica_39_391
PubMedID: 19280383

Title : T-cell activation via CD26 and caveolin-1 in rheumatoid synovium - Ohnuma_2006_Mod.Rheumatol_16_3
Author(s) : Ohnuma K , Inoue H , Uchiyama M , Yamochi T , Hosono O , Dang NH , Morimoto C
Ref : Mod Rheumatol , 16 :3 , 2006
Abstract : CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region. We previously reported that recombinant soluble CD26 enhances peripheral blood T-cell proliferation induced by the recall antigen tetanus toxoid (TT). Recently, we demonstrated that CD26 binds caveolin-1 on antigen-presenting cell (APC), and that residues 201-211 of CD26 along with the serine catalytic site at residue 630, which constitute a pocket structure of CD26/DPPIV, contribute to binding to caveolin-1 scaffolding domain. In addition, following CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, with linkage to NF-kappaB activation, followed by upregulation of CD86. Finally, reduced caveolin-1 expression on APC inhibits CD26-mediated CD86 upregulation and abrogates CD26 effect on TT-induced T-cell proliferation, and immunohistochemical studies revealed an infiltration of CD26+ T cells in the sub-lining region of rheumatoid synovium and high expression of caveolin-1 in the increased vasculature and synoviocytes of the rheumatoid synovium. Taken together, these results strongly suggest that CD26-cavolin-1 interaction plays a role in the upregulation of CD86 on TT-loaded APC and subsequent engagement with CD28 on T cells, leading to antigen-specific T-cell activation such as the T-cell-mediated antigen-specific response in rheumatoid arthritis.
ESTHER : Ohnuma_2006_Mod.Rheumatol_16_3
PubMedSearch : Ohnuma_2006_Mod.Rheumatol_16_3
PubMedID: 16622717

Title : Analysis of mutation of the plasma cholinesterase gene in a man who had died following a traffic accident - Tsuji_2006_Forensic.Sci.Int_159_223
Author(s) : Tsuji A , Inoue H , Kudo K , Ikeda N
Ref : Forensic Science International , 159 :223 , 2006
Abstract : We analyzed mutation of the butyrylcholinesterase (BCHE) gene in a 69-year-old man on whom a forensic autopsy had been performed after he had died following a traffic accident. Extremely low plasma cholinesterase activity had been pointed out by the emergency doctor at the hospital prior to his death and based on this, organophosphorus poisoning had been suspected. However, no pesticides, which could have reduced the plasma cholinesterase activity, were detected by toxicological analysis using GC/MS. Subsequently, one base insertion was found in exon 2. The frame shift mutation had occurred because a homozygous extra T had been inserted between nucleotides 1343 and 1344, resulting in the appearance of a stop codon in codon 454 (AGA454TAA, Arg454stop). This heterozygous frame shift mutation at this point was identified in the man's son. It is likely that there may be many such latent patients with abnormal plasma cholinesterase activity, and accordingly we should always bear this fact in mind and should carry out molecular genetic testing for an accurate diagnosis of this deficiency.
ESTHER : Tsuji_2006_Forensic.Sci.Int_159_223
PubMedSearch : Tsuji_2006_Forensic.Sci.Int_159_223
PubMedID: 16216459

Title : Treatment of hepatocellular carcinoma and the exacerbation of liver function - Okano_2001_Int.J.Oncol_19_1279
Author(s) : Okano H , Shiraki K , Inoue H , Deguchi M , Sugimoto K , Sakai T , Ohmori S , Murata K , Nakano T , Yamakado K , Takeda K
Ref : Int J Oncol , 19 :1279 , 2001
Abstract : We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), selective segmental sclerotherapy (SSS), combined TAE and PEIT, or transcatheter arterial chemo-injection (TAI). Thirteen patients showed an exacerbation of liver function after treatment. The laboratory data on admission, showed the lower levels of serum albumin and cholinesterase in this group. In comparison to patients who did not show any exacerbation of liver function, these 13 patients had undergone combined TAE and PEIT. An analysis of cases after TAE and PEIT treatment revealed that the time from TAE to PEIT was shorter in the exacerbation group than in the non-exacerbation group, however, there was no significant difference in the amount of injected ethanol between the two groups. It is assumed that the values of albumin and cholinesterase before treatment, or the period from TAE to PEIT are related to liver failure after treatment. Combining TAE and PEIT treatment may be effective for HCC, however, we should pay special attention to liver failure after treatment.
ESTHER : Okano_2001_Int.J.Oncol_19_1279
PubMedSearch : Okano_2001_Int.J.Oncol_19_1279
PubMedID: 11713600

Title : Histamine-induced increase in isometric tension of smooth muscle is mediated by local vagus nerve in human bronchus - Aizawa_2000_Respiration_67_652
Author(s) : Aizawa H , Inoue H , Miyazaki N , Hara N
Ref : Respiration , 67 :652 , 2000
Abstract : BACKGROUND: The vagus nerve is reported to play an important role in the regulation of airway responsiveness. OBJECTIVE: In the present study, we investigated the role of the local vagus nerve in the changes in isometric tension of smooth muscle induced by histamine in the human airway.
METHODS: Eight human lung tissue specimens were obtained at thoracic surgery, and 24 bronchial smooth muscle strips were used for isometric tension recording. The changes in isometric tension were induced by histamine in the presence or absence of physostigmine (10(-6) M), atropine (10(-6) M), and/or tetrodotoxin (10(-6) M).
RESULTS: We found that: (1) histamine induced a dose-dependent increase in the isometric tension in human bronchial smooth muscle; (2) physostigmine (10(-6) M) significantly potentiated the amplitude of the histamine-induced increase in isometric tension; (3) atropine (10(-6) M) significantly suppressed the histamine-induced increase in isometric tension; (4) tetrodotoxin (10(-6) M), did not affect the histamine-induced increase in isometric tension of smooth muscle, and (5) in the presence of tetrodotoxin, atropine significantly suppressed the histamine-induced increase in isometric tension. CONCLUSION: These findings suggest that the histamine-induced increase in isometric tension is mediated partly by acetylcholine, presumably released by the direct action of histamine on the vagus efferent nerve terminals without the central reflex via vagus nerve.
ESTHER : Aizawa_2000_Respiration_67_652
PubMedSearch : Aizawa_2000_Respiration_67_652
PubMedID: 11124648

Title : Oral chronic toxicity and carcinogenicity test of polyoxyethylene(10)nonylphenyl ether (NP-10) in female F344 rats - Inoue_1999_J.Toxicol.Sci_2_167
Author(s) : Inoue H , Yamamoto T , Shoji A , Watari N , Hirouchi Y , Enomoto M , Morita K
Ref : Journal of Toxicological Sciences , 2 :167 , 1999
Abstract : Chronic toxicity and carcinogenicity of polyoxyethylene(10)nonylphenyl ether (NP-10) to Fischer 344 rats were investigated using 70 females per group in 4 study groups, or 280 rats in total. Diets containing NP-10 at 0, 1000, 3000 and 9000 ppm were prepared and orally administered to the animals repeatedly for 52 weeks for a chronic toxicity study and for 104 weeks for a carcinogenicity study. Observations of general condition, body weight analysis, food consumption analysis, hematologic examination, blood chemistry examination (only at Week 52 of administration), urinalysis (only at Week 52), ophthalmologic examination (immediately prior to administration and at Week 52), organ weight analysis and pathological examination were performed. The results are summarized as follows. The mean intake of the test substance was 60.5, 182 and 559 mg/kg/day in the chronic toxicity study for 52 weeks and 55.2, 166 and 520 mg/kg/day in the carcinogenicity study for 104 weeks in the 1000, 3000 and 9000 ppm groups, respectively. Mortality decreased approximately in a dose-related manner, with 28% in the control group, 26% in the 1000 ppm group, and 14% each in the 3000 and 9000 ppm groups. In general condition, there were no signs attributed to the treatment with NP-10. Body weight gain was suppressed in the 9000 ppm group throughout the administration period and in the 3000 ppm group during Weeks 21-88. Food consumption decreased in the 9000 and 3000 ppm groups. Food efficiency was lower in the 9000 and 3000 ppm groups. As a result of the hematologic examination, hematocrit value, hemoglobin value, red blood cell count, platelet count and MCV were lower and MCH and MCHC higher in the 9000 ppm group at Week 52 of administration. At Week 104, the neutrophil ratio was higher and lymphocyte ratio lower in the 3000 and 9000 ppm groups, and furthermore, hematocrit value, hemoglobin value, MCV and MCH were slightly lower in the 9000 ppm group. In the blood coagulability tests, prothrombin time was slightly shortened in the 9000 ppm group at Week 52. As a result of the blood chemistry examination, total protein and albumin values were higher and total bilirubin, uric acid and trygliceride value lower in the 3000 ppm and higher dose groups. Furthermore, the free cholesterol value was higher and the values of potassium, cholesterol ester ratio, GOT, GPT, ALP and cholinesterase were lower in the 9000 ppm group. As a result of the urinalysis, the specific gravity of urine was higher and urine pH acidic in some animals. As a result of the ophthalmologic examination, no abnormal animals were found in the 9000 ppm group. As a result of the organ weight analysis, absolute and relative weights of the liver and adrenals were higher in the 3000 and/or 9000 ppm groups as changes which were considered attributable to the test substance and, in addition, organs with a lower absolute weight and higher relative weight with the suppressed body weight gain were observed in the 9000 ppm group. The histopathological examination revealed no marked findings in necropsy observation or histology in the treated groups in the animals killed at Weeks 52, 104 as well as those killed moribund and dead animals. In the histological findings, bile duct hyperplasia of liver in the animals killed at Week 52, proliferative duct of pancreas in the animals killed at Week 104, pigment of deposit in pituitary and angiectasis of adrenals in the animals killed at moribund and dead animals were observed in a slightly larger number in the treated groups, but none of these changes were different in degree from the control and were not considered to be specific lesions. As a result of the overall study of the neoplastic lesions of all animals killed on schedule and of moribund and dead animals, no tumors were found in the treated groups which had increased in occurrence. Based on the above findings, it was determined that the no-adverse-effect level in the chronic toxicity study was 1000 ppm
ESTHER : Inoue_1999_J.Toxicol.Sci_2_167
PubMedSearch : Inoue_1999_J.Toxicol.Sci_2_167
PubMedID: 10664963

Title : Transcriptional regulation of the human choline acetyltransferase gene -
Author(s) : Hersh LB , Inoue H , Li YP
Ref : Prog Brain Res , 109 :47 , 1996
PubMedID: 9009692

Title : The nucleotide and deduced amino acid sequences of porcine liver proline- beta-naphthylamidase. Evidence for the identity with carboxylesterase - Matsushima_1991_FEBS.Lett_293_37
Author(s) : Matsushima M , Inoue H , Ichinose M , Tsukada S , Miki K , Kurokawa K , Takahashi T , Takahashi K
Ref : FEBS Letters , 293 :37 , 1991
Abstract : A cDNA clone for porcine liver proline-beta-naphthylamidase was isolated and sequenced. The deduced amino acid sequence of 567 residues was highly homologous with those of carboxylesterases (EC 3.1.1.1) previously reported for other species. In addition, proline-beta-naphthylamidase purified from porcine liver was shown to have strong activity towards p-nitrophenylacetate, a representative substrate for carboxylesterases. These results suggest that proline-beta-naphthylamidase is identical with carboxylesterase.
ESTHER : Matsushima_1991_FEBS.Lett_293_37
PubMedSearch : Matsushima_1991_FEBS.Lett_293_37
PubMedID: 1959668
Gene_locus related to this paper: pig-EST1