Hypoxia induces PGC-1α expression and mitochondrial biogenesis in the myocardium of TOF patients.
PGC-1alpha, a potent transcriptional coactivator, is the major regulator of mitochondrial biogenesis and activity in the cardiac muscle. The dysregulation of PGC-1alpha and its target genes has been reported to be associated with congenital and acquired heart diseases. By examining myocardium samples from patients with Tetralogy of Fallot, we show here that PGC-1alpha expression levels are markedly increased in patients compared with healthy controls and positively correlated with the severity of cyanosis. Furthermore, hypoxia significantly induced the expression of PGC-1alpha and mitochondrial biogenesis in cultured cardiac myocytes. Mechanistic studies suggest that hypoxia-induced PGC-1alpha expression is regulated through the AMPK signaling pathway. Together, our data indicate that hypoxia can stimulate the expression of PGC-1alpha and mitochondrial biogenesis in the cardiac myocytes, and this process might provide a potential adaptive mechanism for cardiac myocytes to increase ATP output and minimize hypoxic damage to the heart.
Zhu
Lingyun
L
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Wang
Qiang
Q
Zhang
Lin
L
Fang
Zhixiang
Z
Zhao
Fang
F
Lv
Zhiyuan
Z
Gu
Zuguang
Z
Zhang
Junfeng
J
Wang
Jin
J
Zen
Ke
K
Xiang
Yang
Y
Wang
Dongjin
D
Zhang
Chen-Yu
CY
D055372:AMP-Activated Protein Kinases / Q000502:physiology; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction / Q000502:physiology; D013771:Tetralogy of Fallot / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
D015415:Biomarkers; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human