The Octadecaneuropeptide ODN Protects Astrocytes against Hydrogen Peroxide-Induced Apoptosis via a PKA/MAPK-Dependent Mechanism
作者： Yosra Hamdi , Hadhemi Kaddour , David Vaudry , Seyma Bahdoudi , Salma Douiri
DOI: 10.1371/JOURNAL.PONE.0042498
关键词: Protein kinase C 、 Cell biology 、 Metabotropic receptor 、 Receptor antagonist 、 Receptor 、 Molecular biology 、 Adenylyl cyclase 、 MAPK/ERK pathway 、 Biology 、 Astrocyte 、 Phosphorylation
摘要: Astrocytes synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN) an endogenous ligand both central-type benzodiazepine (CBR) metabotropic receptors. We have recently shown that ODN exerts protective effect against hydrogen peroxide (H2O2)-induced oxidative stress in astrocytes. The purpose present study was to determine type receptor transduction pathways involved cultured rat first observed activity at very low concentrations abrogated by antagonist cyclo1–8[DLeu5]OP, but not CBR flumazenil. also found is positively coupled adenylyl cyclase astrocytes glioprotective action upon H2O2-induced astrocyte death PKA- MEK-dependent, PLC/PKC-independent. Downstream PKA, induced ERK phosphorylation, which turn activated expression anti-apoptotic gene Bcl-2 blocked stimulation H2O2 pro-apoptotic Bax. on Bax/Bcl-2 balance contributed abolish deleterious mitochondrial membrane integrity caspase-3 activation. Finally, inhibitory be PKA MEK-dependent. In conclusion, results demonstrate potent involves PKA/ERK-kinase pathway inhibit
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