Overexpression of Tfam protects mitochondria against β‐amyloid‐induced oxidative damage in SH‐SY5Y cells

作者：Shangcheng Xu, Min Zhong, Lei Zhang, Yuan Wang, Zhou Zhou, Yutong Hao, Wenyan Zhang, Xuesen Yang, Aimin Wei, Liping Pei, Zhengping Yu · 发表于：FEBS Journal · 年份：2009 · DOI：10.1111/j.1742-4658.2009.07094.x · 被引用次数：89 · 研究领域：Alzheimer's disease research and treatments、Mitochondrial Function and Pathology、Trace Elements in Health

There is strong evidence that beta-amyloid (Abeta) causes oxidative stress and induces mitochondrial dysfunction in the pathogenesis of Alzheimer's disease. Mitochondrial transcription factor A (Tfam) has multiple roles in the maintenance of mtDNA. To study the protective roles of Tfam against amyloid neurotoxicity, we established SH-SY5Y cell lines stably overexpressing Tfam and exposed them to 10 microm Abeta1-42 for 24 h. We found that Tfam overexpression attenuated Abeta1-42-induced cell viability damage and apoptosis. In addition, Tfam overexpression significantly suppressed the increase in excess reactive oxygen species and reversed the reduction in cytochrome c oxidase activity and ATP production induced by Abeta1-42. Furthermore, overexpression of DeltaC-Tfam, which has no functional domain for stimulating mtDNA transcription but can still maintain the mtDNA nucleoid formation and mtDNA copy number, also exhibited protective effects against Abeta1-42 cytotoxicity in SH-SY5Y cells. Together, our data suggest that Tfam overexpression protects mitochondria against Abeta-induced oxidative damage in SH-SY5Y cells. These beneficial effects may be attributable to the roles of Tfam in maintaining mtDNA nucleoid formation and mtDNA copy number.