15d-Prostaglandin J2 Protects Cortical Neurons Against Oxygen–Glucose Deprivation/Reoxygenation Injury: Involvement of Inhibiting Autophagy Through Upregulation of Bcl-2

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• 作者：Haidong Qin ; Weiguo Tan ; Zheng Zhang ; Lei Bao…
• 关键词：Peroxisome proliferator ; activated receptor ; γ ; Oxygen–glucose deprivation ; Autophagy ; Bcl ; 2 ; Beclin 1
• 刊名：Cellular and Molecular Neurobiology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：35
• 期：3
• 页码：303-312
• 全文大小：1,813 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Animal Anatomy, Morphology and Histology
  
• 出版者：Springer Netherlands
• ISSN：1573-6830

文摘

We have previously shown that PPAR-γ agonist 15d-PGJ2 inhibited neuronal autophagy after cerebral ischemia/reperfusion injury. However, the underlying mechanism of its regulatory role in neuronal autophagy remains unclear. This study was designed to test the hypothesis that 15d-PGJ2 upregulated Bcl-2 which binds to Beclin 1, and thereby inhibits autophagy. We performed cell viability assay, cytotoxicity assay, western blot, and co-immunoprecipitation to analyze autophagy activities in vitro model of oxygen–glucose deprivation/reoxygenation (OGD/R). OGD/R induced autophagy in cultured cortical neurons. 15d-PGJ2 treatment significantly decreased LC3-II/LC3-I ratio and Beclin 1 expression, but increased p62 expression. Autophagic inhibitor 3-methyladenine decreased LC3-II levels, increased neuronal cell viability, and mimicked some protective effect of 15d-PGJ2 against OGD/R injury. OGD/R-induced autophagy coincided with decreases in Bcl-2 expression and increases in Beclin 1 expression.?15d-PGJ2 treatment upregulated Bcl-2 expression and decreased Beclin 1 expression, and inhibit the dissociation of Beclin1 from Bcl-2 significantly. Bcl-2 siRNA abrogated the effect of 15d-PGJ2 on Beclin 1, LC3-II and p62, and influence cell viability and LDH level, while scRNA did not. PPAR-γ agonist 15d-PGJ2 exerts neuroprotection partially via inhibiting neuronal autophagy after OGD/R injury. The inhibition of autophagy by 15d-PGJ2 is mediated through upregulation of Bcl-2.