Ghrelin Inhibits Hydrogen Peroxide-Induced Apoptotic Cell Death of Oligodendrocytes Via ERK and p38MAPK Signaling

H2O2-induced apoptotic cell death of oligodendrocytes is significantly inhibited by ghrelin through increasing ERK activation and decreasing p38MAPK activation, which is dependent on ghrelin receptor. Here, we examined the protective effect of ghrelin on apoptotic cell death induced by hydrogen peroxide (H2O2) in primary oligodendrocyte cultures. Ghrelin receptor, growth hormone secretagogue receptor 1a, was expressed in mature oligodendrocytes. H2O2 (1 mm) treatment induced apoptotic cell death of oligodendrocytes, which was significantly inhibited by ghrelin treatment. Ghrelin also reduced cytochrome c release, and caspase-3 activation increased by H2O2 treatment. Furthermore, the protective effect of ghrelin against H2O2-induced oligodendrocyte cell death was mediated through growth hormone secretagogue receptor 1a. Both ERK and p38MAPK were activated (peaked at 8 h in ERK and 1 h in p38MAPK) by H2O2 treatment, whereas c-Jun N-terminal kinase and Akt were not. Interestingly, ghrelin further increased ERK activation and decreased p38MAPK activation after H2O2 treatment. Next, we tried to elucidate the role of ERK and p38MAPK activation in H2O2-induced apoptotic cell death of oligodendrocytes using pharmacological inhibitors. We found that the inhibition of apoptotic cell death of oligodendrocytes by ghrelin was abolished by ERK inhibitor, PD98059 (20 μM), whereas cell survival was increased by p38MAPK inhibitor, SB203580 (10 μM). These results thus indicate that ghrelin inhibits H2O2-induced oligodendrocytes cell death in part by increasing ERK activation and decreasing p38MAPK activation, and ghrelin may represent a potential therapeutic agent for protecting oligodendrocytes in central nervous system injuries.