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Peroxisome proliferator-activated receptor-gamma dependent pathway reduces the phosphorylation of dynamin-related protein 1 and ameliorates hippocampal injury induced by global ischemia in rats.
Chuang, Yao-Chung; Lin, Tsu-Kung; Yang, Ding-I; Yang, Jenq-Lin; Liou, Chia-Wei; Chen, Shang-Der.
Afiliação
  • Chuang YC; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
  • Lin TK; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
  • Yang DI; Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • Yang JL; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
  • Liou CW; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
  • Chen SD; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
J Biomed Sci ; 23(1): 44, 2016 May 12.
Article em En | MEDLINE | ID: mdl-27175924
BACKGROUND: Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein that, upon phosphorylation at serine 616 (p-Drp1(Ser616)), plays a pivotal role in neuronal death after ischemia. In the present study, we hypothesized that peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent pathway can reduce the expression of p-Drp1(Ser616) and ameliorate hippocampal injury induced by global ischemia in rats. RESULTS: We found that pretreatment of the rats with Mdivi-1, a selective Drp1 inhibitor, decreased the level of transient global ischemia (TGI)-induced p-Drp1(Ser616) and reduced cellular contents of oxidized proteins, activated caspase-3 expression as well as the extent of DNA fragmentation. Delivery of siRNA against Drp1 attenuated the expression of p-Drp1(Ser616) that was accompanied by alleviation of the TGI-induced protein oxidation, activated caspase-3 expression and DNA fragmentation in hippocampal proteins. Exogenous application of pioglitazone, a PPARγ agonist, reduced the p-Drp1(Ser616) expression, decreased TGI-induced oxidative stress and activated caspase-3 expression, lessened the extents of DNA fragmentation, and diminished the numbers of TUNEL-positive neuronal cells; all of these effects were reversed by GW9662, a PPARγ antagonist. CONCLUSIONS: Our findings thus indicated that inhibition of TGI-induced p-Drp1(Ser616) expression by Drp1 inhibitor and Drp1-siRNA can decrease protein oxidation, activated caspase-3 expression and neuronal damage in the hippocampal CA1 subfield. PPARγ agonist, through PPARγ-dependent mechanism and via decreasing p-Drp1(Ser616) expression, can exert anti-oxidative and anti-apoptotic effects against ischemic neuronal injury.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Isquemia Encefálica / Dinaminas / PPAR gama / Região CA1 Hipocampal Limite: Animals Idioma: En Revista: J Biomed Sci Assunto da revista: MEDICINA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Isquemia Encefálica / Dinaminas / PPAR gama / Região CA1 Hipocampal Limite: Animals Idioma: En Revista: J Biomed Sci Assunto da revista: MEDICINA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Taiwan