Journal
CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 35, Issue 3, Pages 303-312Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-014-0125-y
Keywords
Peroxisome proliferator-activated receptor-gamma; Oxygen-glucose deprivation; Autophagy; Bcl-2; Beclin 1
Categories
Funding
- National Natural Science Foundation of China [81000488]
- Fudan University Young Teacher Capability Enhancement Program [20520133268]
- Nanjing Medical Science and Technology Development Program [YKK11124]
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We have previously shown that PPAR-gamma agonist 15d-PGJ(2) 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-PGJ(2) 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-PGJ(2) 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-PGJ(2) against OGD/R injury. OGD/R-induced autophagy coincided with decreases in Bcl-2 expression and increases in Beclin 1 expression. 15d-PGJ(2) 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-PGJ(2) on Beclin 1, LC3-II and p62, and influence cell viability and LDH level, while scRNA did not. PPAR-gamma agonist 15d-PGJ(2) exerts neuroprotection partially via inhibiting neuronal autophagy after OGD/R injury. The inhibition of autophagy by 15d-PGJ(2) is mediated through upregulation of Bcl-2.
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