https://scholars.lib.ntu.edu.tw/handle/123456789/564608
標題: | Impairment of oxidative stress-induced heme oxygenase-1 expression by the defect of Parkinson-related gene of PINK1 | 作者: | MING-JEN LEE Chien W.-L. Lee T.-R. Hung S.-Y. Kang K.-H. WEN-MEI FU |
公開日期: | 2011 | 卷: | 117 | 期: | 4 | 起(迄)頁: | 643-653 | 來源出版物: | Journal of Neurochemistry | 摘要: | Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Mutation in the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene causes an autosomal recessive form of PD. However, the etiology related to PINK1 is still not clear. Here, we examined the effect of PINK1 on heme oxygenase (HO)-1 induction in SH-SY5Y neuronal cells following H 2O 2 or 1-methyl-4-phenylpyridinium (MPP +) treatment. The HO-1 induction in response to H 2O 2 and MPP + treatment was impaired by the expression of recombinant PINK1 G309D mutant. PINK1 G309D mutation increased the apoptosis of SH-SY5Y cells following H 2O 2 treatment and cell survival was rescued by the over-expression of HO-1 using adenovirus (Ad) infection. In addition, knockdown of tumor necrosis factor receptor-associated protein-1 (TRAP1), which is the substrate of PINK1 kinase, in SH-SY5Y cells also inhibited the expression of HO-1 in response to oxidative stress. The up-regulation of TRAP1 expression following H 2O 2 treatment was inhibited by the expression of recombinant PINK1 G309D mutant. The H 2O 2-induced HO-1 induction was Akt- and ERK-dependent. The phosphorylation of ERK and Akt but not p38 was inhibited in cells expressing the PINK1 G309D mutant and knockdown of TRAP1. These results indicate a novel pathway by which the defect of PINK1 inhibits the oxidative stress-induced HO-1 production. Impairment of HO-1 production following oxidative stress may accelerate the dopaminergic neurodegeneration in Parkinson patients with PINK1 defect. ? 2011 The Authors. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/564608 | ISSN: | 223042 | DOI: | 10.1111/j.1471-4159.2011.07229.x | SDG/關鍵字: | heme oxygenase 1; mitogen activated protein kinase; phosphatase and tensin homolog induced putative kinase 1; protein kinase B; regulator protein; tumor necrosis factor receptor associated factor 1; unclassified drug; apoptosis; article; cell survival; controlled study; enzyme induction; enzyme phosphorylation; enzyme synthesis; gene mutation; human; human cell; neuropathology; oxidative stress; Parkinson disease; priority journal; protein expression; protein function; signal transduction; 1-Methyl-4-phenylpyridinium; Adenoviridae; Benzimidazoles; Blotting, Western; Cell Line; Cell Survival; Cloning, Molecular; Coloring Agents; Dopamine; Fluorescent Antibody Technique; Fluorescent Dyes; Gene Expression Regulation; Genetic Vectors; Heme Oxygenase-1; HSP90 Heat-Shock Proteins; Humans; L-Lactate Dehydrogenase; Mutation; Oxidative Stress; Parkinson Disease, Secondary; Protein Kinases; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tetrazolium Salts; Thiazoles; Adenoviridae |
顯示於: | 藥理學科所 |
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