期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 228, 期 6, 页码 1238-1248出版社
WILEY-BLACKWELL
DOI: 10.1002/jcp.24277
关键词
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资金
- National Natural Science Foundation of China [30930105, 81120108002]
- CMB Distinguished Professorships Award [F510000/G16916404]
- Natural Science Foundation of the Education Bureau of Shaanxi Province [2012JZ4001]
Mitochondrial biogenesis disorders appear to play an essential role in cardiac dysfunction. Acetylcholine as a potential pharmacologic agent exerts cardioprotective effects. However, its direct action on mitochondria biogenesis in acute cardiac damage due to ischemia/reperfusion remains unclear. The present study determined the involvement of mitochondrial biogenesis and function in the cardiopotection of acetylcholine in H9c2 cells subjected to hypoxia/reoxygenation (H/R). Our findings demonstrated that acetylcholine treatment on the beginning of reoxygenation improved cell viability in a concentration-dependent way. Consequently, acetylcholine inhibited the mitochondrial morphological abnormalities and caused a significant increase in mitochondrial density, mass, and mitochondrial DNA (mtDNA) copy number. Accordingly, acetylcholine enhanced ATP synthesis, membrane potentials, and activities of mitochondrial complexes in contrast to H/R alone. Furthermore, acetylcholine stimulated the transcriptional activation and protein expression of peroxisome proliferator-activated receptor co-activator 1 alpha (PGC-1, the central factor for mitochondrial biogenesis) and its downstream targets including nuclear respiration factors and mitochondrial transcription factor A. In addition, acetylcholine activated phosphorylation of AMP-activated protein kinase (AMPK), which was located upstream of PGC-1. Atropine (muscarinic receptor antagonist) abolished the favorable effects of acetylcholine on mitochondria. Knockdown of PGC-1 or AMPK by siRNA blocked acetylcholine-induced stimulating effects on mtDNA copy number and against cell injury. In conclusion, we suggested, acetylcholine as a mitochondrial nutrient, protected against the deficient mitochondrial biogenesis and function induced by H/R injury in a cellular model through muscarinic receptor-mediated, AMPK/PGC-1-associated regulatory program, which may be of significance in elucidating a novel mechanism underlying acetylcholine-induced cardioprotection. J. Cell. Physiol. 228: 12381248, 2013. (c) 2012 Wiley Periodicals, Inc.
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