Ghrelin Antagonized 1-Methyl-4-Phenylpyridinium (MPP+)-Induced Apoptosis in MES23.5 Cells
Ghrelin Antagonized 1-Methyl-4-Phenylpyridinium (MPP+)-Induced Apoptosis in MES23.5 Cells
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DOI：
10.1007/s12031-008-9162-7
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发表时间：
2009-02-01
影响因子：
3.1
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
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作者：
Dong, Juanjuan;Song, Ning;Jiang, Hong
Ghrelin是生长激素促分泌素受体（GHS-R）的内源性配体，其作用是刺激生长激素释放。在前期研究中，我们观察了Ghrelin对1-甲基-4-苯基-1，2，3，6-四氢吡啶治疗的帕金森病小鼠体内多巴胺能神经元的保护作用。为了阐明潜在的机制，在本研究中，我们在1-甲基-4-苯基吡啶（MPP+）处理的能够表达GHS-R1 a的MES 23. 5细胞中进行了体外实验。10 - 1，000 μ mol/L MPP+处理导致细胞活力降低，乳酸脱氢酶渗漏增加。选择200 μ mol/L MPP+处理进行进一步的试验。200 μ mol/L MPP+处理的MES 23.5细胞显示线粒体跨膜电位降低，活性氧化物质产生水平升高，caspase-3活化。此外，这些细胞还表现出凋亡的形态学变化。不同浓度的ghrelin（10（-12）~ 10（-7）mol/L）预处理可抑制MPP+诱导的细胞凋亡，且呈剂量依赖性。结果提示Ghrelin可拮抗MPP+诱导的MES 23.5细胞凋亡。ghrelin的保护作用涉及线粒体功能的恢复。
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.