Ghrelin Antagonized 1-Methyl-4-Phenylpyridinium (MPP+)-Induced Apoptosis in MES23.5 Cells

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) acting to stimulate growth hormone release. In the previous study, we have observed the neuroprotective effects of ghrelin on dopaminergic neurons in vivo in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -treated Parkinson's disease mice. In order to illustrate the underlying mechanisms, in the present study, we conducted our experiment in vitro in 1-methyl-4-phenylpyridinium (MPP+)-treated MES23.5 cells that could express GHS-R1a. Ten- to 1,000-mu mol/L MPP+ treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-mu mol/L MPP+ treatment was chosen to do the further experiments. MES23.5 cells treated with 200 mu mol/L MPP+ showed decreased mitochondrial transmembrane potential, an elevated level of reactive oxidative species production and activation of caspase-3. Additionally, these cells also showed apoptotic morphological changes. Pretreatment with different doses of ghrelin (10(-12)-10(-7) mol/L) could abolish the MPP+-induced apoptotic changes in a dose-dependent manner. These results suggested that ghrelin could antagonize MPP+-induced apoptosis in MES23.5 cells. The protective effects of ghrelin involved the restoration of mitochondria function.