The effect of melatonin on MPP+-induced mitochondrial fission and Drp1 expression

• Main Authors: I-Ling Pan, 潘伊玲
• Other Authors: Jih-Ing Chuang
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/08338446043875546226

碩士 === 國立成功大學 === 生理學研究所 === 96 === Mitochondrial dysfunction and oxidative stress are involved in pathogenesis of Parkinson’s disease (PD). 1-methyl-4-phenylpyridinium (MPP+), an inhibitor of mitochondrial complex I, induces oxidative insults on nigrostriatal dopaminergic neurodegeneration and parkinsonism in primates. Mitochondrial morphology is dynamic change and precisely regulated by the mitochondrial fission and fusion machinery. Human Fis1 (hFis1) and the translocation of dynamin-related protein 1 (Drp1) regulate mitochondrial fission, whereas the mitochondrial fusion is regulated by mitofusin 1/2 (Mfn1/2) and optic atrophy 1 (OPA1). The role of Drp1-regulated mitochondrial fission was demonstrated by the results showing that cells overexpressing dominant-negative Drp1K38A were resistant to reactive oxygen species-induced toxicity. Furthermore, our previous studies showed that melatonin functioned as an antioxidant to prevent MPP+-induced neuronal death. However, the effect of melatonin on mitochondrial morphology remains unknown. We therefore investigate whether Drp1 is involved in MPP+-induced mitochondrial fission and the protective effect of melatonin. We found that MPP+-induced oxidative stress, mitochondrial fission, mitochondrial Drp1 upregulation and consequently cell death. Furthermore, we currently observed that overexpressing EGFP-Drp1 in neurons promoted mitochondrial fission, however, overexpression of EGFP-Drp1K38A in neurons blocked MPP+-induced mitochondrial fission and cell death. Moreover, melatonin co-treatment significantly prevented MPP+-induced oxidative insults, mitochondrial fission, mitochondrial Drp1 upregulation and cell death. The results suggest that MPP+ induced oxidative stress, Drp1-mediated mitochondrial fission and finally cell death. However, co-treatment with melatonin and MPP+ protected neurons from MPP+ toxicity through reducing oxidative stress and mitochondrial fission.