Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells.
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.
Xu
Shangcheng
S
Department of Occupational Health, Third Military Medical University, Chongqing, China.
Zhong
Min
M
Zhang
Lei
L
Wang
Yuan
Y
Zhou
Zhou
Z
Hao
Yutong
Y
Zhang
Wenyan
W
Yang
Xuesen
X
Wei
Aimin
A
Pei
Liping
L
Yu
Zhengping
Z
D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D018628:Gene Dosage; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D010446:Peptide Fragments; C499631:TFAM protein, human; D014157:Transcription Factors; C075222:amyloid beta-protein (1-42); D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV