期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 226, 期 4, 页码 1052-1059出版社
WILEY
DOI: 10.1002/jcp.22424
关键词
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资金
- National Natural Science Foundation of China [30930105, 30873058, 30770785]
- National Basic Research Program of China [2007CB512005]
- CMB Distinguished Professorships Award [F510000/G16916404]
Recent findings have reported that up-regulation of tumor necrosis factor-alpha (TNF-alpha) induced by myocardial hypoxia aggravates cardiomyocyte injury. Acetylcholine (ACh), the principle vagal neurotransmitter, protects cardiomyocytes against hypoxia by inhibiting apoptosis. However, it is still unclear whether ACh regulates TNF-alpha production in cardiomyocytes after hypoxia. The concentration of extracellular TNF-alpha was increased in a time-dependent manner during hypoxia. Furthermore, ACh treatment also inhibited hypoxia-induced TNF-alpha mRNA and protein expression, caspase-3 activation, cell death and the production of reactive oxygen species (ROS) in cardiomyocytes. ACh treatment prevented the hypoxia-induced increase in p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, and increased extracellular signal-regulated kinase (ERK) phosphorylation. Co-treatment with atropine, a non-selective muscarinic acetylcholine receptor antagonist, or methoctramine, a selective type-2 muscarinic acetylcholine (M-2) receptor antagonist, abrogated the effects of ACh treatment in hypoxic cardiomyocytes. Co-treatment with hexamethonium, a non-selective nicotinic receptor antagonist, and methyllycaconitine, a selective alpha7-nicotinic acetylcholine receptor antagonist, had no effect on ACh-treated hypoxic cardiomyocytes. In conclusion, these results demonstrate that ACh activates the M-2 receptor, leading to regulation of MAPKs phosphorylation and, subsequently, down-regulation of TNF-alpha production. We have identified a novel pathway by which ACh mediates cardioprotection against hypoxic injury in cardiomyocytes. J. Cell. Physiol. 226: 1052-1059, 2011. (C) 2010 Wiley-Liss, Inc.
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