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Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis 被引量:6
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作者 Xing-Nian Zhou Quan Zhang +6 位作者 Hong Peng Yu-Jie Qin Yu-Hong Liu Lu Wang Ming-Liang Cheng Xin-Hua Luo Hong Li 《World Journal of Gastroenterology》 SCIE CAS 2024年第11期1588-1608,共21页
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b... BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF. 展开更多
关键词 Silent information regulator sirtuin 1 Ferroptosis PYROPTOSIS p53/glutathione peroxidase 4/gasdermin D Acute liver failure
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Evaluation of Glutathione Peroxidase Enzymatic Activity in Seminal Plasma of Patients Treated at the Institute Pasteur in Cote d’Ivoire
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作者 Marie Florence N’Guessan Bi Bali Sery +4 位作者 Foua Jonas Vanié Bi N’Gbesso Amos Ekissi Youzan Ferdinand Djohan Founzégué Amadou Coulibaly Allico Joseph Djaman 《Advances in Reproductive Sciences》 2023年第4期116-126,共11页
Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the... Glutathione peroxidase (GPx) is an antioxidant that plays an important role in the maintenance of male fertility. The aim of this study was to compare the profile of enzymatic activity of glutathione peroxidase in the seminal plasma of normozoosperm and those of pathological sperm. Thus, the activity of glutathione peroxidase was determined in the seminal plasma of 20 normozoosperms, 9 azoosperms and 31 oligoasthenoteratozoosperms. It was 37.58 ± 3.14 U/L in normozoosperms, 39.39 ± 2.27 U/L in oligoasthenoteratozoosperms, and 29.77 ± 2.62 U/L in azoosperms. The mean GPx enzyme activity of normozoosperms did not differ significantly from that of oligoasthenoteratozoosperms and azoosperms. In contrast, comparison of enzyme activity between abnormal sperms gave a significant difference. This study showed that glutathione peroxidase enzymatic activity is not related to sperm quality. 展开更多
关键词 glutathione peroxidase ANTIOXIDANT OLIGOASTHENOTERATOZOOSPERMIA AZOOSPERMIA Normozoospermia
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Evaluation of combined detection of nuclear factor erythroid 2-related factor 2 and glutathione peroxidase 4 in primary hepatic carcinoma and preliminary exploration of pathogenesis
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作者 JIE DUAN AIDONG GU +5 位作者 WEI CHEN CHANGHAO CHEN FANGNAN SONG FAXI CHEN FANGFANG JIANG HUIWEN XING 《BIOCELL》 SCIE 2023年第12期2609-2615,共7页
This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2... This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2(NRF2)and glutathione peroxidase 4(GPX4)in primary hepatic carcinoma(PHC).Methods:The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC.The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup.Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased,and the expression of NRF2 and GPX4 in the cells was determined.NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2,and changes in cell proliferation and invasion capabilities were observed.Results:The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH(p<0.05),and the two indicators combined was excellent in diagnosing PHC.Moreover,patients with high expression of NRF2 and GPX4 had a higher risk of death(p<0.05).In in vitro experiments,both NRF2 and GPX4 expression was elevated in HepG2(p<0.05).HepG2 activity was enhanced by increasing the expression of the two,vice versa(p<0.05).Conclusion:NRF2 and GPX4 combined is excellent in diagnosing PHC,and promotes the malignant development of PHC. 展开更多
关键词 Nuclear factor erythroid 2 Related factor 2 glutathione peroxidase 4 Primary hepatic carcinoma Clinical significance Mechanism of action PATHOGENESIS
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Glutathione peroxidase mimicry of diphenyl diselenide: Plausible contribution of proteins’ thiols
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作者 Ebenezer Morayo Ale Steve Osagie Asuelimen Olawale Otitoju 《Toxicology Advances》 2023年第2期14-20,共7页
Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organ... Organoseleniums are a class of compounds attracting attention across the globe owing to their Glutathione peroxidase(GPx)mimicry,which confers on them a strong antioxidant activity.Diphenyl diselenide(DPDS)is an Organoselenium whose GPx mimetic property has been suggested to rely on the oxidation of non-protein or protein thiols critical to the activities of some sulfhydryl enzymes.This study,therefore investigated the GPx mimic/antioxidant property of DPDS as well as the role of thiols of two key sulfhydryl enzymes,cerebral Na^(+)/K^(+)-ATPase(sodium pump)and hepatic delta-aminolevulinic acid dehydratase(δ-ALAD)in the GPx mimicry of DPDS.Albino Wistar rats were euthanized,and the liver and brain were removed and used to assay for the effect of DPDS on lipid peroxidation induced by two prooxidants[Fe2^(+)(10μM)and H2O2,(1 mM)]as well as the activities of the sulfhydryl enzymes.The results revealed that DPDS profoundly(P<0.05)counteracted Fe2^(+)and H2O2-induced lipid peroxidation in the rats’hepatic and cerebral tissues.Furthermore,the results of assay systems for lipid peroxidation and sodium pump revealed that DPDS inhibited Na^(+)/K^(+)-ATPase and lipid peroxidation in the brain tissue homogenates in the same reaction system.A similar result was obtained in the assay system for lipid peroxidation and hepaticδ-ALAD as DPDS simultaneously inhibited the enzyme’s activity and lipid peroxidation.This suggests that the GPx mimetic property of DPDS may be linked to the enzymes’loss of activity,which further validates the suggestions that the enzymes’inhibition,as well as the antioxidant action of DPDS,rely on the oxidation of critical thiols of the enzymes.However,the GPx mimicry of DPDS should be investigated in the presence of thiol-blocking or oxidizing agents in biological systems in order to further ascertain the role of protein thiols. 展开更多
关键词 Organoseleniums diphenyl diselenide glutathione peroxidase ANTIOXIDANT THIOLS delta-aminolevulinic acid dehydratase Na^(+)/K^(+)-ATPase
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Cloning of catalase and expression patterns of catalase and selenium-dependent glutathione peroxidase from Exopalaemon carinicauda in response to low salinity stress 被引量:6
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作者 REN Hai LI Jian +4 位作者 LI Jitao YING Yu GE Hongxing LI Dongli YU Tianji 《Acta Oceanologica Sinica》 SCIE CAS CSCD 2015年第8期52-61,共10页
Catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GPx) play a vital role in protecting organisms against various oxidative stresses by eliminating H202, The objective of this paper is to evaluate th... Catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GPx) play a vital role in protecting organisms against various oxidative stresses by eliminating H202, The objective of this paper is to evaluate the roles of these antioxidant molecules in the ridgetail white prawn Exopalaemon carinicauda in response to low salinity stress. A complementary DNA (cDNA) containing the complete coding sequence of CAT was cloned from the hepatopancreas using reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. The full-length cDNA of CAT (2 649 bp) contains a 5'-untranslated region (UTR) of 78 bp, a 3'- UTR of 1 017 bp, with a poly (A) tail, and an open reading frame of 1 554 bp encoding a 517-amino-acid polypeptide with predicted molecular mass of 58.46 kDa and estimated isoelectric point of 6.64. This CAT sequence contained the proximal active site signature (60FDRERIPERWHAKGAG76), proximal heme-ligand signature sequence (350RLFSYPDTH358) and three catalytic amino acid residues (His71, Asn144 and Tyr354). Sequence comparison showed that the CAT deduced amino acid sequence of E. carinicauda shared 68%-92% of identities with those of other species. Quantitative real-time PCR analysis revealed that CAT mRNA was widely expressed in the hepatopancreas (highest), hemocyte, eyestalk, heart, gill, muscle, ovary and stomach. Under low salinity stress, CAT and GPx mRNA expression levels both in the gill and hepatopancreas increased significantly at the first 48 h and 6 h respectively, indicating a tissue- and time-dependent antioxidant response in E. carinicauda. All these results indicate that E. carinicauda CAT is a member of the CAT family and might be involved in the acute response against low salinity stress. 展开更多
关键词 Exopalaemon carinicauda catalase (CAT) selenium-dependent glutathione peroxidase (Se-GPx) CLONING expression
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Artesunate Effect on Schistosome Thioredoxin Glutathione Reductase and Cytochrome c Peroxidase as New Molecular Targets in Schistosoma mansoni-infected Mice 被引量:2
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作者 Amany A.Abdin Dalia S.Ashour Zeinab S.Shoheib 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2013年第12期953-961,共9页
Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of ... Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis. 展开更多
关键词 SCHISTOSOMIASIS ARTESUNATE PRAZIQUANTEL Thioredoxin glutathione reductase Cytochrome c peroxidase
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Glutathione peroxidase activity in cell cultures from different regions of human epididymis 被引量:2
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作者 Enrique Castellon Hernan Rioseco +4 位作者 Juan Rojas Michel Royer Eduardo Salas Hoctor Contreras Christian Huidobro 《Asian Journal of Andrology》 SCIE CAS CSCD 2005年第1期33-37, ,共5页
Aim: To study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis. Methods: Tissue was obtained from patients undergoing therapeutic orchide... Aim: To study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis. Methods: Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Epithelial cell cultures were obtained from the caput, corpus and cauda epididymides. Enzymatic activity was measured in conditioned media by colorimetric methods in absence or presence of 1, 10 or 100 nrnoI.L^(-1) testosterone. The effect of 1 μmol.L^(-1) flutamide was also evaluated. Results: GPx activity was higher in cultures from corpus and cauda than caput epididymidis. The presence of different concentrations of testosterone increase enzyme activity in cell cultures from all epididymal regions. Addition of flutamide reverses the androgen dependent increase of GPx activity. Conclusion: GPx activity is secreted from human epididymal cells in a region dependent manner and is regulated by androgens. 展开更多
关键词 glutathione peroxidase human epididymis cell culture androgen regulation
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Glutathione Peroxidase Revisited—Simulation of the Catalytic Cycle by Computer-Assisted Molecular Modelling 被引量:6
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作者 K. -D. AUMANN N. BEDORF +3 位作者 R. BRIGELIUS-FLOHED D. SCHOMBURG AND L. FLOHE(Gesellschaft fur Biotechnologische Forschung mbH (GBF) Mascheroder Weg 1, D-38124 Braunschweig, Germany Deutsches Institut fur Ernahrungsforschung (DIfE) Arthur-Scheunert-Allee 114 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1997年第2期136-155,共20页
Glutathione peroxidase, the first example of selenoproteins identified in mammals, was subjected to force field calculations and molecular dynamics in order to enable a clearer comprehension of enzymatic selenium cata... Glutathione peroxidase, the first example of selenoproteins identified in mammals, was subjected to force field calculations and molecular dynamics in order to enable a clearer comprehension of enzymatic selenium catalysis. Starting from the established X-ray structure of bovine GPX, all kinetically defined intermediates and enzyme substrate complexes were modelled. The models thus obtained support the hypothesis that the essential steps of the catalysis are three distinct redox changes of the active site selenium which, in the ground state, presents itself at the surface of selenoperoxidases as the center of a characteristic triad built by selenocysteine, glutarnine and tryptophan. In GPX, four arginine residues and a lysine residue provide an electrostatic architecture which, in each reductive step, directs the donor substrate GSH towards the catalytic center in such a way that 1ts sulfhydryl group must react with the selenium moiety. To this end, different equally efficient modes of substrate binding appear possible. The models are consistent with substrate specificity data, kinetic pattern and other functional characteristics of the enzyme. Comparison of molecular models of GPX with those of other members of the GPX superfamily reveals that the cosubstrate binding mechanisrns are unique for the classical type of cytosolic glutathione peroxidases but cannot operate e. g. in plasma GPX and phospholipid hydroperoxide GPX. The structural differences between the selenoperoxidases, shown to be relevant to their specificities, are discussed in terms of functional diversification within the GPX superfamily 展开更多
关键词 GPX glutathione peroxidase Revisited Simulation of the Catalytic Cycle by Computer-Assisted Molecular Modelling
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Expression and Chromosomal Mapping of Mouse Gpx2 Gene Encoding the Gastrointestinal Form of Glutathione Peroxidase, GPX-GI 被引量:5
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作者 FONG-FONG CHU R. STEVEN ESWORTHY +4 位作者 YE SHIH HO MARGIT BERMEISTER KRISTINE SWIDEREK AND ROSEMARY W. ELLIOTT(Department of Medical Oncology, City of Hope Midical Center, Duarte,CA91010, USA Department of Psychiatry and Human Genetics,Mintal Health Research 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1997年第2期156-162,共7页
GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI ... GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestmal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment.By analyzing a panel of mouse mterspecies DNA from the Jackson Laboratory's backcross resource,we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7.Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express GPx1 gene 展开更多
关键词 GPX-GI GPx GENE FORM Expression and Chromosomal Mapping of Mouse Gpx2 Gene Encoding the Gastrointestinal Form of glutathione peroxidase GI
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Glutathione peroxidase, superoxide dismutase and catalase activities in children with chronic hepatitis 被引量:2
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作者 Nagwa Abdallah Ismail Sawsan H. Okasha +3 位作者 Anil Dhawan Azza M. O. Abdel Rahman Nehal Abdel Hamid Olfat Shaker 《Advances in Bioscience and Biotechnology》 2012年第7期972-977,共6页
The advantages of measuring hepatic oxidative status in liver biopsy are that it helps in diagnosis of hepatic dysfunction, reflects the degree of deterioration in the liver tissues, and helps to determine the severit... The advantages of measuring hepatic oxidative status in liver biopsy are that it helps in diagnosis of hepatic dysfunction, reflects the degree of deterioration in the liver tissues, and helps to determine the severity of hepatic injury. We aimed to study the oxidative stress state in children with chronic hepatitis by using indirect approach in which antioxidant enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) are determined in the liver tissue. The present study included 21 children and adolescents (12 males, 9 females) suffering from chronic hepatitis. Patients were selected from the Hepatology Clinic, New Children’s Hospital, Cairo University from November 2006 till 2009 and compared with a group of 7 children who happened to have incidental normal liver biopsy. Children with chronic hepatitis had mean age 8.12 ± 1.15 years. It was further subdivided into 2 subgroups: chronic viral heaptitis (n = 13) and cryptogenic hepatitis (n = 8). GPX, SOD and CAT levels were measured in fresh liver tissue (cell free homogenates) using ELISA. In chronic hepatitis group;there was a significant increase in the hepatic GPX activity (38.59 ± 35.82 nmol/min/ml) as compared to the control group (10.62 ± 6.68 nmol/min/ml). Also a significant correlation was observed between SOD and both ALT (r = 0.87, p < 0.05) and AST (r = 0.74, p < 0.05). GPX correlated with ALT (r = 0.80, p < 0.05) level in the chronic viral hepatitis subgroup. Our findings suggest that oxidative stress could play a role in the pathogenesis of chronic hepatitis. These preliminary results are encouraging to conduct more extensive clinical studies combining antioxidant therapy with various treatments. 展开更多
关键词 glutathione peroxidase Superoxide DISMUTASE CATALASE Chronic HEPATITIS Oxidative Stress
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Novel Selenium-containing Human Single-chain Variable Fragment with Glutathione Peroxidase Activity from Computer-aided Molecular Design 被引量:1
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作者 WANG Cheng WAN Pei +9 位作者 GONG Ping-sheng LV Li-min XU Ya-wei ZHAO Yang HE Bo ZHAO Gang YAN Gang-lin MU Ying LV Shao-wu LUO Gui-min 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2011年第5期813-819,共7页
In order to enhance the glutathione peroxidase(GPX) catalytic activity of the selenium-containing single-chain variable fragments(Se-scFv), a novel human scFv was designed on the basis of the structure of human an... In order to enhance the glutathione peroxidase(GPX) catalytic activity of the selenium-containing single-chain variable fragments(Se-scFv), a novel human scFv was designed on the basis of the structure of human antibody and optimized via bioinformatics methods such as homologous sequence analysis, three-dimensional(3D) model building, binding-site analysis and docking. The DNA sequence of the new human scFv was synthesized and cloned into the expression vector pET22b(+), then the scFv protein was expressed in soluble form in Escherichia coli BL21(DE3) and purified by Ni2+-immobilized metal affinity chromatography(IMAC). The serine residue of scFv in the active site was converted into selenocysteine(Sec) with the chemical modification method, thus, the human Se-scFv with GPX activity was obtained. The GPX activity of the Se-scFv protein was characterized. Compared with other Se-scFv, the new human Se-scFv showed similar efficiency for catalyzing the reduction of hydrogen peroxide by glutathione. It exhibited pH and temperature dependent catalytic activity and a typical ping-pong kinetic mechanism. 展开更多
关键词 glutathione peroxidase(GPX) Single-chain variable fragment(scFV) Three-dimensional model SELENIUM
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Effect of 2-Selenium Bridged β-Cyclodextrin,Glutathione Peroxidase Mimic on Stroke of Stroke-prone Spontaneously Hypertensive Rats 被引量:1
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作者 JIAZhi-dan SUNYe +3 位作者 MUYing MAJi-sheng YANGang-lin LUOGui-min 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2004年第3期328-333,共6页
To investigate the treatment effect of 2-selenium bridged β -cyclodextrin(2-SeCD),a GPX mimic,on the stroke of stroke-prone spontaneously hypertensive rats(SHRSP),fifty-two SHRSP of 8-week old were randomly divided i... To investigate the treatment effect of 2-selenium bridged β -cyclodextrin(2-SeCD),a GPX mimic,on the stroke of stroke-prone spontaneously hypertensive rats(SHRSP),fifty-two SHRSP of 8-week old were randomly divided into four groups A,B,C and control group D. The rats of groups A,B,C and D were given 1.0%-1.5% NaCl mass fraction as drinking fluid. After onset of stroke,groups A,B and C were given \{orally\} 16.05,160.5 and 1605 mg·kg -1 ·day -1 of 2-SeCD,respectively,and group D was given water for \{2 weeks.\} The clinical score of stroke,systolic blood pressure(SBP),survival time of rats were recorded and the histopathologic examinations of their brain and carotid artery were made after decapitation. The clinical scores of stroke after treatment with 160.5 mg·kg -1 ·day -1 (Group B) and 1605 mg·kg -1 ·day -1 (Group C) of 2-SeCD are 2.55±0.98 and 1.98±0.79,respectively,those are obviously lower than that of group D(3.41±0.83,p<0.01). The survival days in group B(10.0±8.6) and group C(14.4±7.9) are longer than that for group D(4.7±2.9,p<0.01). The electron microscope study showed that the endothelium of carotid artery was near to normal in group B and group C,while it was seriously injured in control group D and mildly injured in group A. 2-SeCD may effectively be used to treat the stroke for SHRSP. 展开更多
关键词 2-Selenium bridged β -cyclodextrin glutathione peroxidase Enzyme mimic STROKE Stroke-prone Spontaneously hypertensive rat
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Selenium Regulation of Selenium-dependent Glutathione Peroxidases in Animals and Transfected CHO Cells 被引量:2
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作者 ROGER A. SUNDE BRITTA M. THOMPSON +3 位作者 MELANIE D. PALM SHERRI L.WEISS KEVIN M. THOMPSON AND JACQUELINE K. EVENSON(Nutritional Sciences Program and Department of Biochemistry,University of Missouri, Columbia MO 65211 USA) 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 1997年第2期346-355,共10页
Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se ... Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se requirements. We have continued to study Se regulation of GPX1 to better understand the underlying mechanism and to gain insight into how cells themselves regulate nutrient status. In progressive Se deficiency in rats, GPX1 activity,protein and mRNA all decrease in a dramatic, coordinated and exponential fashion such that Se-deficient GPX1 mRNA levels are 6-15% of Sexadequate levels. mRNA levels for other Sedependent proteins are far less decreased in the same animals. The mRNA levels for a second Se-dependent peroxidase, phospholipid hydroperoxide glutathione peroxidase (GPX4 ), are little affected by Se deficiency, demonstrating that Se regulation of GPX1 is unique. Se regulation of GPX1 activity in growing male and female rats shows that the Se requirernent is 100 ng/g diet, based on liver GPX1 activity; use of GPX1 mRNA as the parameter indicates that the Se requirement is nearer to 50 ng Se/g diet in both male and female rats. This approach will readily detect an altered dietary Se requirement, as shown by the incremental increases in dietary Se requirement by 150, 100 or 50 ng Se/g diet in Seudeficient rat pups repleted with Se for 3, 7 or 14 d, respectively. Studies with CHO cells stably transfected with recombinant GPX1 also show that overexpression of GPX1 does not alter the minimum level of media Se necessary for Se-adequate levels of GPX1 activity or mRNA. We hypothesize that classical GPX1 has an integral biological role in the mechanism used by cells to regulate Se status,making GPX1 an especially useful and effective parameter for determining Se requirements in animals 展开更多
关键词 GPX mRNA Selenium Regulation of Selenium-dependent glutathione peroxidases in Animals and Transfected CHO Cells CHO
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Glutathione S-transferase M1 polymorphism and esophagealcancer risk:An updated meta-analysis based on 37 studies 被引量:4
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作者 Quan-Jun Lu Ya-Cong Bo +7 位作者 Yan Zhao Er-Jiang Zhao Wolde Bekalo Sapa Ming-Jie Yao Dan-Dan Duan Yi-Wei Zhu Wei-Quan Lu Ling Yuan 《World Journal of Gastroenterology》 SCIE CAS 2016年第5期1911-1918,共8页
AIM: To evaluate the relationship between glutathione S-transferase M1(GSTM1) polymorphism and susceptibility to esophageal cancer(EC).METHODS: A comprehensive search of the United States National Library of Medicine ... AIM: To evaluate the relationship between glutathione S-transferase M1(GSTM1) polymorphism and susceptibility to esophageal cancer(EC).METHODS: A comprehensive search of the United States National Library of Medicine Pub Med database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC"(until November 1, 2014). The statistical analysis was performed using the SAS software(v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software(v.5.0; Oxford, England); crude odds ratios(ORs) with 95% confidence intervals(CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC.RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this metaanalysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations(OR = 1.33, 95%CI: 1.12-1.57, P_(heterogeneity) < 0.000001, and I2 = 77.0%), particularly in the Asian population(OR = 1.53, 95%CI: 1.26-1.86, P_(heterogeneity)< 0.000001, and I2 = 77.0%), but not in the Caucasian population(OR = 1.02, 95%CI: 0.87-1.19, P_(heterogeneity) = 0.97, and I2 = 0%).CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations. 展开更多
关键词 META-analysis glutathione S-transferaseM1 POLYMORPHISM ESOPHAGEAL cancer DELETIONS
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Synthesis and Kinetics of a Novel Mimic with Glutathione Peroxidase Activity—Tellurium-containing Hyaluronic Acid (TeHA)
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作者 Zhi Bo CHEN Bo Xun ZHANG +7 位作者 Zhong Xiu HUANG Qing Lin PENG Jia CHEN Yu WANG Jian Guo ZHANG Guang Zhi JIANG Wen Shu LI Lan Ying LIU 《Chinese Chemical Letters》 SCIE CAS CSCD 2006年第7期969-972,共4页
A novel mimic was synthesized by modifying hyaluronic acid (HA) with tellurium, whose function is similar to that of glutathione peroxidase (GPX). The structure of TeHA was characterized by means of IR and NMR, th... A novel mimic was synthesized by modifying hyaluronic acid (HA) with tellurium, whose function is similar to that of glutathione peroxidase (GPX). The structure of TeHA was characterized by means of IR and NMR, the target-Te was located at -CH2OH of the N-acetyl-D- glucosamine of HA. The H202 reducing activity of TeHA, by glutathione (GSH), was 163.6 U/μmol according to Wilson's method. In contrast to other mimics, TeHA displayed the highest activity. Moreover, TeHA accepted many hydroperoxides as its substrates, such as H2O2, cumenyl hydroperoxide (CuOOH) and tert-butyl hydroperoxide (t-BuOOH), and CuOOH was the optimal substrate of TeHA. A ping-pong mechanism was observed in the steady-state kinetic studies of the reactions catalyzed by TeHA. 展开更多
关键词 Hyaluronic acid TELLURIUM glutathione peroxidase SYNTHESIS kinetics.
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Changes of Selenium Metabolism Glutathione Peroxidase Activity and Lipid Peroxides Content in Severely Scalding-injured Rats
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作者 刘泽军 董燕麟 《Journal of Medical Colleges of PLA(China)》 CAS 1989年第3期213-216,共4页
The changes of sclenium metabolism, glutathione peroxidase activity and lipid peroxidescontent in the tissues of rats suffering from 30% TBSA full thickness scalding were observed in thefirst 7 days after injury. It w... The changes of sclenium metabolism, glutathione peroxidase activity and lipid peroxidescontent in the tissues of rats suffering from 30% TBSA full thickness scalding were observed in thefirst 7 days after injury. It was found that selenium content in the rat tissues decreased remarkably af-ter injury, which in turn resulted in serious reduction of glutathione peroxidasc activity and significantincrease of lipid peroxides in the scrum, crythrocytcs and liver. However the muscular tissue showedno significant changes. These facts imply that after burn injury, the body is in a state of selenium deficiency, the lossof selenium might be responsible for the reduction of anti - peroxidation ability of glutathioneperoxidase, and conscqucntly there is an increase of lipid peroxides in the tissues. Only the musculartissue is insensitive to lipid peroxidation. It is believed that the reduction of anti-peroxidation abilityof glutathione peroxidasc after bum injury might be one of the main causes to intensify, the injury re-suiting from free radicals. 展开更多
关键词 SELENIUM METABOLISM glutathione peroxidase lipid peroxide SCALDING injury rat
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Synthesis and Characterization of Specific Haptens Used to Generate Abzyme with Glutathione Peroxidase Activity
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作者 Liu Jun-qiu Gao Shu-juan +1 位作者 Luo Gui-min Shen Jia-cong 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 1998年第3期55-57,共3页
Glutathione was modified selectively by 2,4 dinitrochlorobenzene,giving S substituted dinitrophenyl glutathione(GSH S DNP).GSH S DNP was further esterified by iso butanol,hexanol,cyclohexanol and benzyl alcohol.Four h... Glutathione was modified selectively by 2,4 dinitrochlorobenzene,giving S substituted dinitrophenyl glutathione(GSH S DNP).GSH S DNP was further esterified by iso butanol,hexanol,cyclohexanol and benzyl alcohol.Four haptens used to generate abzyme with glutathione peroxidase(GPX)activity were synthesized.They are GSH DNP biesters:GSH DNP di iso butyl ester(GSH DNP IBU),GSH DNP bihexyl ester(GSH DNP HE),GSH DNP bicyclohexyl ester(GSH DNP CH),GSH DNP bibenzylmethyl ester(GSH DNP BE).The structures of the haptens were characterized by means of elemental analysis,IR and 1H NMR. 展开更多
关键词 glutathione peroxidase ABZYME HAPTEN
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Urea-induced Inactivation and Unfolding of Recombinant Phospholipid Hydroperoxide Glutathione Peroxidase from Oryza sativa
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作者 WANG Feng ZHOU Hui-ping +3 位作者 KONG Bao-hua FAN Jing-hua CHEN Hai-ru LIU Jin-yuan 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2007年第5期562-566,共5页
Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst... Phospholipid hydroperoxide glutathione peroxidase is an antioxidant enzyme that has the highest capability of reducing membrane-bound hydroperoxy lipids as compared to free organic and inorganic hydroperoxides amongst the glutathione peroxidases.In this study,urea-induced effects on the inactivation and unfolding of a recombinant phospholipid hydroperoxide glutathione peroxidase(PHGPx)from Oryza sativa were investigated by means of circular dichroism and fluorescence spectroscopy.With the increase of urea concentration,the residual activity of OsPHGPx decreases correspondingly.When the urea concentration is above 5.0 mol/L,there was no residual activity.In addition,the observed changes in intrinsic tryptophan fluorescence,the binding of the hydrophobic fluorescence probe ANS,and the far UV CD describe a common dependence on the concentration of urea suggesting that the conformational features of the native OsPHGPx are lost in a highly cooperative single transition.The unfolding process comprises of three zones:the native base-line zone between 0 and 2.5 mol/L urea,the transition zone between 2.5 and 5.5 mol/L urea,and the denatured base-line zone above 5.5 mol/L urea.The transition zone has a midpoint at about 4.0 mol/L urea. 展开更多
关键词 Circular dichroism Fluorescence Conformational change Phospholipid hydroperoxide glutathione peroxidase(PHGPx) Urea titration
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Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide,glutathione peroxidase,and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury
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作者 Qingde Wang Guixiang Cui +2 位作者 Hongxia Liu Yizhao Li Fengshan Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2008年第11期1233-1236,共4页
BACKGROUND: Several studies have demonstrated that low molecular weight heparin-superoxide dismutase (LMWH-SOD) conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anti... BACKGROUND: Several studies have demonstrated that low molecular weight heparin-superoxide dismutase (LMWH-SOD) conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE: To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide (NO), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING: A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS: A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation (sham-operated group). Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS: Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups: physiological saline, LMWH-SOD, SOD, LMWH + SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD (20 000 U/kg) and LMWH (LMWH dose calculated according to weight ratio, LMWH: SOD = 23.6:51), and LMWH (dose as in the LMWH + SOD group) were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES: Serum levels of NO, MPO, and GSH-Px. RESULTS: Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO (P 〈 0.01). The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group (P 〈 0.01), compared with the physiological saline group (P 〈 0.05-0.01). Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group (P 〈 0.01). Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group (P 〉 0.05). CONCLUSION: In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level. 展开更多
关键词 cerebral ischemia/reperfusion nitric oxide MYELOperoxidase glutathione peroxidase low molecular weight heparin-superoxide dismutase conjugate
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STUDIES ON BLOOD GLUTATHIONE PEROXIDASE PROTEIN LEVEL OF CHILDREN IN KESHAN DISEASE AND KASHIN-BECK DISEASE AREAS
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作者 Tan Wuhong(谭武红) +9 位作者 Zhong Xiaohong(种晓红) Yang Zhantian(杨占田) Zhai Lianbang(翟连榜) Wang Lixin(王立新) Xu Guanglu(徐光禄) 《Academic Journal of Xi'an Jiaotong University》 2002年第2期133-135,共3页
Objective To oberve the change in blood glutathione peroxidase (GSH-Px) protein levels of residents in the low-selenium (Se) area by contrasting the blood GSH-Px protein level of the children in the Keshan disease are... Objective To oberve the change in blood glutathione peroxidase (GSH-Px) protein levels of residents in the low-selenium (Se) area by contrasting the blood GSH-Px protein level of the children in the Keshan disease area with those in the Kashin-Beck disease and non-endemic areas. Methods GSH-Px protein levels were measured by enzyme-linked immunosorbent assays (ELISA). The Se content and GSH-Px activity were assayed by the 2,3-diaminonaphthalene spectrofluorimetric method and glutathione reductase-coupled method respectively. Results ①The blood Se content and GSH-Px protein level of children in Keshan disease area (Moding) were significantly lower than those in Xi’an non-endemic area, however, there was no significant difference when compared with the low-Se non-endemic area; ②The blood Se content, GSH-Px activity and GSH-Px protein level of children in the Kashin-Beck disease area (Yulin) were significantly lower than those of children in two non-endemic areas and in the Keshan disease area; ③The blood Se content and GSH-Px activity were positively correlated to the GSH-Px protein level respectively. Conclusion These results indicate that the blood GSH-Px protein level is decreased in the low-Se residents. The Se status not only affects the GSH-Px activity but also regulate the GSH-Px protein level. 展开更多
关键词 Kashan DISEASE Kashin-Beck DISEASE CHILDREN glutathione peroxidase PROTEIN
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