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-micromol/L MPP(+) treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-micromol/L MPP(+) treatment was chosen to do the further experiments. MES23.5 cells treated with 200 micromol/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.
Dong
Juanjuan
J
State Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao, China.
Song
Ning
N
Xie
Junxia
J
Jiang
Hong
H
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D054439:Ghrelin / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D054440:Receptors, Ghrelin / Q000378:metabolism
D054439:Ghrelin; D018696:Neuroprotective Agents; D054440:Receptors, Ghrelin; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium