Ghrelin inhibits hydrogen peroxide-induced apoptotic cell death of oligodendrocytes via ERK and p38MAPK signaling

Abstract

Here, we examined the protective effect of ghrelin on apoptotic cell death induced by hydrogen peroxide (H 2O 2) in primary oligodendrocyte cultures. Ghrelin receptor, growth hormone secretagogue receptor 1a, was expressed in mature oligodendrocytes. H 2O 2 (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 H 2O 2 treatment. Furthermore, the protective effect of ghrelin against H 2O 2-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 H 2O 2 treatment, whereas c-Jun N-terminal kinase and Akt were not. Interestingly, ghrelin further increased ERK activation and decreased p38MAPK activation after H 2O 2 treatment. Next, we tried to elucidate the role of ERK and p38MAPK activation in H 2O 2-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 H 2O 2-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. Copyright © 2011 by The Endocrine Society.