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Acetylcholine inhibits hypoxia-induced tumor necrosis factor-α production via regulation of MAPKs phosphorylation in cardiomyocytes.
J Cell Physiol. 2011 Apr; 226(4):1052-9.JC

Abstract

Recent findings have reported that up-regulation of tumor necrosis factor-alpha (TNF-α) 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-α production in cardiomyocytes after hypoxia. The concentration of extracellular TNF-α was increased in a time-dependent manner during hypoxia. Furthermore, ACh treatment also inhibited hypoxia-induced TNF-α 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-α production. We have identified a novel pathway by which ACh mediates cardioprotection against hypoxic injury in cardiomyocytes.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20857413

Citation

Li, Dong-Ling, et al. "Acetylcholine Inhibits Hypoxia-induced Tumor Necrosis Factor-α Production Via Regulation of MAPKs Phosphorylation in Cardiomyocytes." Journal of Cellular Physiology, vol. 226, no. 4, 2011, pp. 1052-9.
Li DL, Liu JJ, Liu BH, et al. Acetylcholine inhibits hypoxia-induced tumor necrosis factor-α production via regulation of MAPKs phosphorylation in cardiomyocytes. J Cell Physiol. 2011;226(4):1052-9.
Li, D. L., Liu, J. J., Liu, B. H., Hu, H., Sun, L., Miao, Y., Xu, H. F., Yu, X. J., Ma, X., Ren, J., & Zang, W. J. (2011). Acetylcholine inhibits hypoxia-induced tumor necrosis factor-α production via regulation of MAPKs phosphorylation in cardiomyocytes. Journal of Cellular Physiology, 226(4), 1052-9. https://doi.org/10.1002/jcp.22424
Li DL, et al. Acetylcholine Inhibits Hypoxia-induced Tumor Necrosis Factor-α Production Via Regulation of MAPKs Phosphorylation in Cardiomyocytes. J Cell Physiol. 2011;226(4):1052-9. PubMed PMID: 20857413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetylcholine inhibits hypoxia-induced tumor necrosis factor-α production via regulation of MAPKs phosphorylation in cardiomyocytes. AU - Li,Dong-Ling, AU - Liu,Jin-Jun, AU - Liu,Bing-Hang, AU - Hu,Hao, AU - Sun,Lei, AU - Miao,Yi, AU - Xu,Hai-Fei, AU - Yu,Xiao-Jiang, AU - Ma,Xin, AU - Ren,Jun, AU - Zang,Wei-Jin, PY - 2010/9/22/entrez PY - 2010/9/22/pubmed PY - 2011/3/3/medline SP - 1052 EP - 9 JF - Journal of cellular physiology JO - J Cell Physiol VL - 226 IS - 4 N2 - Recent findings have reported that up-regulation of tumor necrosis factor-alpha (TNF-α) 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-α production in cardiomyocytes after hypoxia. The concentration of extracellular TNF-α was increased in a time-dependent manner during hypoxia. Furthermore, ACh treatment also inhibited hypoxia-induced TNF-α 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-α production. We have identified a novel pathway by which ACh mediates cardioprotection against hypoxic injury in cardiomyocytes. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/20857413/Acetylcholine_inhibits_hypoxia_induced_tumor_necrosis_factor_α_production_via_regulation_of_MAPKs_phosphorylation_in_cardiomyocytes_ L2 - https://doi.org/10.1002/jcp.22424 DB - PRIME DP - Unbound Medicine ER -