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Role of Peroxisome Proliferator-Activated Receptor Gamma in Glucose-induced Insulin Secretion

Acta Biochimica et Biophysica Sinica 2006年第1期38卷 1-7页

作者： Ze-Kuan XU~(1,2),Neng-Guin CHEN~1,Chang-Yan MA~1,Zhuo-Xian MENG~1,Yu-Jie SUN~1,and Xiao HAN~(1*) ~1 Key Laboratory of Human Functional Genomics of Jiangsu Province,department of Biochemistry and Molecular Biology, nanjing medical university,nanjing 210029,china ~2 department of normal surgery,the first affiliated hospital of nanjing medical university,nanjing 210029,china Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular Biology Nanjing Medical University Nanjing 210029 China department of normal surgery the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Peroxisome proliferator-activated receptor (PPAR) isoforms (α and γ) are known to beexpressed in pancreatic islets as well as in insulin-producing cell *** of PPAR have been shoWn toenhance glucose-induced insulin secretion in rat pancreatic ***,their effect on insulin secretionis still *** understand the molecular mechanism by which PPAR7 exerts its effect on glucose-induced insulin secretion,we examined the endogenous activity of PPAR isoforms,and studied the PPARyfunction and its target gene expression in INS-1 *** found that:(1)endogenous PPARγ was activatedin a ligand-dependent manner in INS-1 cells;(2)overexpression of PPARy in the absence of PPARγ ligandsenhanced glucose-induced insulin secretion,which indicates that the increased glucose-induced insulin secretionis a PPARγ-mediated event;(3)the addition of both PPARγ and retinoid X receptor (RXR) ligands showed asynergistic effect on the augmentation of reporter activity,suggesting that the hetero-dimerization of PPAR7and RXR is required for the regulation of the target genes;(4)PPARs upregulated both the glucose transporter2 (GLUT2) and Cbl-associated protein (CAP) genes in INS-1 *** findings suggest an importantmechanistic pathway in which PPARγ enhances glucose-induced insulin secretion by activating the expressionof GLUT2 and CAP genes in a ligand-dependent manner.

关键词： PPARγ ligand glucose-induced insulin secretion glucose transporter 2 Cb1-associated protein

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Mitochondrial rRNA and tRNA and hearing function

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Cell Research 2007年第3期17卷 227-239页

作者： Guangqian Xing~1 Zhibin Chen~1 Xin Cao~2 ~1department of Otolaryngology,the first affiliated hospital of nanjing medical university,nanjing 210029,china ~2department of Biotechnology,nanjing medical university,nanjing 210029,china department of Otolaryngology the First Affiliated Hospital of Nanjing Medical University Nanjing China department of Biotechnology Nanjing Medical University Nanjing China

The human ear is a delicate sensory apparatus of hearing for normal communication,and its proper functioning is highlydependent on mitochondrial oxidative *** first mitochondrial point mutation for nonsyndromic andaminoglycoside-induced hearing loss was identified in *** then a number of inherited mitochondrial mutationshave been implicated in hearing *** of the molecular defects responsible for mitochondrial disorder-associatedhearing loss are mutations in the 12S rRNA gene and tRNA *** this review,after a short description of normal hear-ing mechanisms and mitochondrial genetics,we outline the recent advances that have been made in the identification ofdeafness-associated mitochondrial mutations,and discuss how mitochondrial dysfunction contributes to hearing loss.

关键词： mitochondrial DNA rRNA tRNA gene mutation aminoglycosides hearing loss

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Mycophenolic acid inhibits SLE-associated cytokine expression and promotes apoptosis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus

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Acta Pharmacologica Sinica 2006年第8期27卷 1051-1057页

作者： Ding-lei SU~(2,3) Hui-juan WANG~2 Xiao-hui JI~(2,5) Yuan-yuan LI~4 Heng-bao XUAN~4 Chun HENG~4 Yu-feng LI~4 ~2department of Immunology,nanjing medical university,nanjing 210029,china:~3department of Hematology,nanjing first hospital affiliated to nanjing medical university,nanjing 210029,china ~4department of Hematology,affiliated Huai'an first hospital of nanjing medical university,Huai'an 223300.china department of Immunology Nanjing Medical University Nanjing China department of Hematology Nanjing First Hospital Affiliated to Nanjing Medical University Nanjing China department of Hematology Affiliated Huai'an First Hospital of Nanjing Medical University Huai'an China

Aim:To investigate the effect of the novel immunosuppressant mycophenolicacid（MPA）on cytokine production and apoptosis of the peripheral blood mono-nuclear cells（PBMC）of patients with systemic lupus erythematosus（SLE）.Methods:The levels of IL-10,IL-12,IFN-γ,sFas and sFasL in the supernatants ofcultured PBMC from 41 SLE patients was determined by the ABC-ELISA *** percentage of IFN-γIL- 10-,IFN-γ-IL-10+,and IFN-γ+IL-10+subsets in CD4+ceils were detected by three-color flow *** percentage of apoptoticTh cells was detected by AV-FITC/PI flow *** from 22 sex-andage-comparable healthy people were used as normal ***:The lev-els of IL-10,IL-12,and IFN-γwere all significantly elevated in the supernatants ofcultured PBMC from SLE samples,compared with normal *** enhancedproductions of IL-10,IL-12,and IFN-γ by PBMC from SLE both spontaneouslyand stimulated by phytohaemagglutinin（PHA）were significantly reduced by *** percentages of CD4+IFN-γIL-10+and CD4+IFN-γ+IL-10+cell subsets in cul-tured PBMC from SLE were significantly increased,but decreased when MPA wasadded into the *** being cultured in vitro for 48h,the PBMC of SLEpatients showed a higher secretion of sFasL as well as a higher percentage *** significantly increased the apoptotic percentage of SLE PBMC,but reduced the secretion of sFasL and ***:MPA reduces theabnormal production of SLE-associated cytokines,such as IL-10,IL-12,and IFN-γ,inhibits the increase of CD4+IFN-γ+IL-10,CD4+IFN-γIL-10+and CD4+IFN-γ+IL-10+subset;and promotes the apoptosis of PBMC in SLE patients,which may beassociated with the therapeutic mechanism of MPA for SLE.

关键词： systemic lupus erythematosus mycophenolic acid cytokine apoptosis therapeutic mechanism

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Mitochondrial uncoupling protein 2 expression in colon cancer and its clinical significance

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World Journal of Gastroenterology 2010年第45期16卷 5773-5778页

作者： Xiao-Yi Kuai, Ze-Yu Ji, Hong-Jie Zhang,department of Gastroenterology, first affiliated hospital of nanjing medical university, nanjing 210029, Jiangsu Province, china department of Gastroenterology First Affiliated Hospital of Nanjing Medical University 300 Guangzhou Road Nanjing 210029 Jiangsu Province China.

AIM: To detect the expression of mitochondrial uncoupling protein 2 (UCP2) in colon cancer and analyze the relation between UCP2 expression and clinical pathological features of colon ***: Fifteen colon tissue samples and 15 its adjacent tissue samples were obtained from colon cancer patients during surgical interventions. UCP2 expression was detected with immunohistochemical method in 10 normal controls, 10 hyperplastic polyp patients, 20 tubular adenoma patients and 78 colon cancer patients. Patients with rectal cancer were excluded. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect UCP2 expressions in colon cancer tissue samples and its adjacent tissue samples. Relation between UCP2 expression and clinical pathological features of colon cancer was also analyzed. RESULTS: The UCP2 mRNA expression level was fourfold higher in colon cancer tissue samples than in its adjacent tissue samples. The UCP2 protein expression level was three-fold higher in colon cancer tissue samples than in its adjacent normal tissue samples. The UCP2 was mainly expressed in cytoplasm. The UCP2 was not expressed in normal colon mucosa. Strong positive staining for UCP2 with a diffuse distribution pattern was identified throughout the mucosa in colon cancer tissue samples with a positive expression rate of 85.9%. The UCP2 expression level was higher in colon cancer tissue samples at clinical stages Ⅲ and Ⅳ than in those at stageⅠ+ Ⅱ. Univariate analysis showed that the high UCP2 expression level was significantly correlated to colon cancer metastasis (hazard ratio = 4.321, confidence interval = 0.035-0.682, P = 0.046). CONCLUSION: UCP2 is highly expressed in human colon cancer tissue and may be involved in colon cancer metastasis.

关键词： Mitochondrial uncoupling protein 2 Colon cancer Uncoupling protein 2 Clinicopathologic characteristics

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Thrombolytic efficacy of native recombinant staphylokinase on femoral artery thrombus of rabbits

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Acta Pharmacologica Sinica 2007年第1期28卷 58-65页

作者： Chun-jian LI~1 Jun HUANG Zhi-jian YANG Ke-jiang CAO department of Cardiology,the first affiliated hospital of nanjing medical university,nanjing 210029,china department of Cardiology the First Affiliated Hospital of Nanjing Medical University Nanjing China

Aim:To investigate the thrombolytic efficacy,ideal dosage and administration ofnative recombinant staphylokinase(r-SAK).Methods:Forty New Zealand rab-bits were randomly assigned into the control,r-SAK low-dose,medial-dose,high-dose,single bolus,allied therapy,recombinant streptokinase(r-SK)and uroki-nase(UK)*** right femoral artery thrombosis models were made byballoon injury,and 120 min after the injury,the thrombolytic agents were infusedthrough the rabbits’ parallel-ear ***:(1)2 h after balloon injury,thepulse pressures of the right femoral arteries reduced to 0 or less than 10% of thatof left femoral arteries in all groups;(2)after thrombolytic therapy,the pulsepressures in some of the femoral arteries markedly enhanced to more than 50% ofthat of left femoral arteries;(3)the reopening rates in the r-SAK medial and high-dose groups were significantly higher than that of the *** reopening rateof the same dose native r-SAK was significant higher than that of UK and r-SK;(4)the patency score of the right femoral arteries tended to be better in the r-SAKmedial and high-dose groups than that of the low-dose group,and the time toreopening in the allied therapy group tended to be ***:(1)r-SAKhas a definite thrombolytic effect on the femoral artery thrombus of rabbits;(2)single bolus is an effective manner of r-SAK therapy,and r-SAK allied therapywith heparin may shorten the time to recanalization;(3)the efficacy of the samedose native r-SAK was superior to that of r-SK and UK.

关键词： recombinant staphylokinase recombinant streptokinase urokinase thrombolytic therapy

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Aberrant methylation frequency of TNFRSF10C promoter in pancreatic cancer cell lines

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Hepatobiliary & Pancreatic Diseases International 2011年第1期10卷 95-100页

作者： Hui-Hua Cai,Yue-Ming Sun,Yi Miao,Wen-Tao Gao,Quan Peng,Jie Yao and Han-Lin Zhao department of General surgery,first affiliated hospital, nanjing medical university,nanjing 210029,china department of General surgery, Jiangsu Province hospital of Traditional Chinese Medicine,nanjing 210029, china department of General surgery First Affiliated Hospital Nanjing Medical University Nanjing 210029 China department of General surgery Jiangsu Province Hospital of Traditional Chinese Medicine Nanjing 210029 China

BACKGROUND:A growing body of evidence suggests that many tumors are initiated by both epigenetic abnormalities and gene mutations,which promote tumor progression. Epigenetic abnormalities include changes in DNA methylation and in the modification of *** study aimed to assess the status of methylation in the CpG island(CGI)of the tumor necrosis factor receptor superfamily member 10c(TNFRSF10C) with combined bisulfite restriction analysis(COBRA)and to evaluate its role in the progression of pancreatic cancer(PC). METHODS:The methylation status of four PC cell lines was assessed using COBRA and/or bisulfite genomic sequencing (BGS).Changes in methylation and TNFRSF10C expression in PC cell lines before and after treatment with 5-aza-2’-deoxycytidine(5-aza-dC)and/or trichostatin A(TSA)were assessed by BGS and real-time *** in the four cell lines was tested by flow cytometry(FCM)and TUNEL assay. RESULTS:The methylation status of the TNFRSF10C promoter was assessed in PC cells(BxPC-3:68.84±8.71%;CFPAC-1:0; PANC-1:96.77±4.57%;SW1990:54.97±7.33%)with the COBRA assay,which was confirmed by the results of *** treatment with 5-aza-dC and/or TSA,apoptosis was induced in PC cells to different degrees,and the levels of TNFRSF10C transcriptional expression in the PC cell lines(except CFPAC-1) increased markedly after 5-aza-dC treatment. CONCLUSIONS:A high frequency of CGI methylation in the TNFRSF10C promoter results in inactivation of the gene and enhancement of tumor growth in most PC cell lines(except CFPAC-1).Inactivation of TNFRSF10C by CGI hypermethylation can play an important role in PC progression and be potentially useful as a diagnostic marker and a new therapeutic approach for PC.

关键词： methylation CpG island pancreatic cancer TNFRSF10C

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Role of 11-beta-hydroxysteroid dehydrogenase type 1 in differentiation of 3T3-L1 cells and in rats with diet-induced obesity

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Acta Pharmacologica Sinica 2006年第5期27卷 588-596页

作者： Yun LIU~(2,3) Wen-lan SUN~3 Yan SUN~3 Gang HU~(2,4) Guo-xian DING~(3,4) ~2department of Pharmaeology,nanjing medical university,nanjing 210029,china ~3department of Geratology,the first hospital affiliated to Nan jinx,medical university,nanjing 210008,china department of Pharmacology Nanjing Medical University Nanjing China department of Geratology the First Hospital Affiliated to Nanjing Medical University Nanjing China

Aim:To observe the roles of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in in vitro preadipocyte differentiation and in rats with diet-induced obe-sity (DIO).Methods:Protein expression of 11β-HSD1 in the process of 3T3-L1 celldifferentiation and in various tissues of the rats were detected by Western blotanalysis;expression of 11β-HSD1 mRNA and glucocorticoid receptor (GR) andother marker genes of preadipocyte differentiation were detected by using real-time ***:Lipid droplets in 3T3-L1 cells accumulated and increased afterstimulation.A dramatically elevated protein level of 11β-HSD1,especially in thelate stages of 3T3-L1 cell differentiation,was *** relative mRNA levelsof 11β-HSD1,GR and cell differentiation markers LPL,aP2,and FAS wereupregulated,and Pref-1 was downregulated during the *** DIO rats,bodyweight,visceral adipose mass index and the protein expression of 11β-HSD1increased,especially in adipose tissue,brain and *** insulin,triglyceride,total cholesterol and low-density lipoprotein cholesterol were foundto be increased in DIO rats,but without any obvious changes in blood glucose ortumor necrosis factor-α ***:11β-HSDI may promote preadipocytedifferentiation,and may be involved in the development of obesity.

关键词： 11-beta-hydroxysteroid dehydrogenase type 1 glucocorticoids adipocytes cell differentiation obesity

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11 beta-hydroxysteroid dehydrogenase type 1 promotes differentiation of 3T3-L1 preadipocyte

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Acta Pharmacologica Sinica 2007年第8期28卷 1198-1204页

作者： Yun LIU~(2,3,4) Yan SUN~(2,4) Ting ZHU~2 Yu XIE~2 Jing YU~2 Wen-lan SUN~2 Guo-xian DING~(2,5) Gang HU~(3,5) ~2department of Geratology the first affiliated hospital,nanjing medical university,nanjing 210008,china ~3department of Pharmacology,nanjing medical university,nanjing 210029,china department of Geratology the First Affiliated Hospital Nanjing Medical University Nanjing China department of Pharmacology Nanjing Medical University Nanjing China

Aim:To investigate the relationship between 11 beta-hydroxysteroid dehydroge-nase type 1(1 lbeta-HSD1),a potential link between obesity and type 2 diabetes,and preadipocyte ***:Mouse 1 lbeta-HSD 1 siRNA plasmidswere transfected into 3T3-L1 preadipocytes(a cell line derived from mouseSwiss3T3 cells that were isolated from mouse embryo),for examination of theeffect of targeted 11 beta-HSD 1 inhibition on differentiation of 3T3-L 1 ***-ferentiation was stimulated with 3-isobutyl-l-methyxanthine,insulin,*** transcription level of the genes was detected by ***:Lipid accumulation was significantly inhibited in cells transfectedwith mouse 1 lbeta-HSD1 siRNA compared with non-transfected 3T3-L1 *** lipid droplets were detected in the transfected cells both prior to stimulationand after stimulation with differentiation-inducing *** expression ofadipocyte differentiation-associated markers such as lipoprotein lipase and fattyacid synthetase were downregulated in the transfected ***,the expres-sion of preadipocyte factor-1,an inhibitor of adipocyte differentiation,wasdownregulated upon stimulation of differentiation and had no changes in thetransfected ***:11 beta-HSD1 can promote *** on this,we propose that 11 beta-HSD1 may be an importantcandidate mediator of obesity and obesity-induced insulin resistance.

关键词： 11 beta-hydroxysteroid dehydrogenase type 1 siRNA 3T3-L1 cell differentiation obesity

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Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab~1 fragment

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Acta Pharmacologica Sinica 2006年第2期27卷 237-241页

作者： Jun LI~1 Xue-hao WANG Xiao-ming WANG Zhao-lai CHEN Division of Hepatic surgery.department of surgery,the first affiliated hospital of nanjing medical university and Jiangsu Province hospital.nanjing 210029.china Division of Hepatic surgery Department of Surgery the First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital Nanjing China

Aim:To perform a site-specific conjugation of Fab’ fragments of a mouse mono-clonal antibody(MoAb)B43(of IgG1subtype)to a bifunctional chelator 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N′,N″,N′″-tetraacetic acid(BAT)via the thiol groups in the hinge distal to the antigen-binding site of the Fab~***:B43 was cleaved using a simple 2-step ***,stable F(ab~1)2was produced by pepsin ***~1 with tree thiol in thehinge region was then obtained by cysteine reduction of F(ab~1)***,a site-specific conjugation of Fab~1 to thiol-specific BAT was performed in a ***:The Fab~1 fragment had approximately 1.8 free thiol groups permolecule after cysteine *** conjugation efficiency and the chemicalyield were approximately 1.28 moles chelator/Fab′ and 74% of the initial concentra-tion of Fab′,*** F(ab′)2,Fab′ and Fab′-BAT all maintained reason-able antigen-binding properties.67Cu labeling of the conjugate under standardconditions did not impair the immunoreactivity of Fab′-***:This isa simple and efficient method for producing immunoreactive conjugates of Fab′-BAT,which can be used to make radiometal-labeled conjugates for further diag-nostic and therapeutic applications.

关键词： conjugation BAT chelator monoclonal antibody

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Association of the MTHFR C677T polymorphism and bone mineral density in postmenopausal women:a meta-analysis

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The Journal of Biomedical Research 2010年第6期24卷 417-423页

作者： Donghua Li,Jie Wu department of Obstetrics and Gynecology,the first affiliated hospital of nanjing medical university,nanjing 210029,Jiangsu Province,china department of Obstetrics and Gynecology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China.

Osteoporosis is a condition characterized by low bone mineral density （BMD） and micro-architectural changes in the bone *** risk of osteoporosis is partly determined by genetic *** role of C677T polymorphism of methylenetetrahydrofolate reductase （MTHFR） gene has been investigated in postmenopausal ***,the relationship between MTHFR polymorphism and BMD is still *** carried out a meta-analysis of 5,833 subjects to evaluate the association of MTHFR and BMD in postmenopausal *** of MEDLINE,Web of Science,Scopus and CNKI were retrieved for all publications relating to MTHFR polymorphism and BMD in postmenopausal *** eligible studies were selected for *** these articles studied the association of MTHFR polymorphism and BMD of the femoral neck and lumbar spine in postmenopausal *** analysis suggested that postmenopausal women with the TT genotype had lower femoral neck BMD than the women with the CC/CT genotype,and the weighted mean difference （WMD） was-0.01 g/cm 2 [95% confidence interval （CI）：（-0.01,-0.01）,P 0.01].However,BMD of the lumbar spine of postmenopausal women with the TT genotype was not significantly different from that of women with the CC/CT *** the random effects model,the WMD between the TT and TC/CC genotype was-0.01 g/cm 2 [95% CI：（-0.04,0.01）,P=0.32].The C677T polymorphism of the MTHFR gene is associated with BMD of the femoral neck in postmenopausal *** with the TT genotype of the MTHFR gene have lower BMD,suggesting that the TT genotype may be a risk factor for postmenopausal osteoporosis.

关键词： methylenetetrahydrofolate reductase postmenopausal women bone mineral density meta-analysis

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