title: 15d-prostaglandin J2 protects cortical neurons against oxygen-glucose deprivation/reoxygenation injury: involvement of inhibiting autophagy through upregulation of Bcl-2.
abstract: 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.
authors.affiliation: Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, 215300, Jiangsu, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 of Changle Road, Nanjing, 210006, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, 68 of Changle Road, Nanjing, 210006, Jiangsu, China. zizhengwangtg@163.com.
authors.forename: Zizheng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C477819:15-deoxyprostaglandin J2; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D005947:Glucose; D015230:Prostaglandin D2