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N -n-butyl haloperidol iodide ameliorates cardiomyocytes hypoxia/reoxygenation injury by extracellular calcium-dependent and -independent mechanisms

Oxidative Medicine and Cellular Longevity, ISSN: 1942-0994, Vol: 2013, Page: 912310
2013
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Article Description

N-n-butyl haloperidol iodide (F) has been shown to antagonize myocardial ischemia/reperfusion injury by blocking calcium channels. This study explores the biological functions of ERK pathway in cardiomyocytes hypoxia/reoxygenation injury and clarifies the mechanisms by which F ameliorates cardiomyocytes hypoxia/reoxygenation injury through the extracellular-calcium-dependent and -independent ERK1/2-related pathways. In extracellularcalcium-containing hypoxia/reoxygenation cardiomyocytes, PKC and ERK1/2 were activated, Egr-1 protein level and cTnI leakage increased, and cell viability decreased. The ERK1/2 inhibitors suppressed extracellular-calcium- containing-hypoxia/reoxygenation-induced Egr-1 overexpression and cardiomyocytes injury. PKC inhibitor downregulated extracellularcalcium-containing-hypoxia/ reoxygenation-induced increase in p-ERK1/2 and Egr-1 expression. F downregulated hypoxia/reoxygenation-induced elevation of p-PKC, p-ERK1/2, and Egr-1 expression and inhibited cardiomyocytes damage. The ERK1/2 and PKC activators antagonized F's effects. In extracellular-calcium-free- hypoxia/reoxygenation cardiomyocytes, ERK1/2 was activated, LDH and cTnI leakage increased, and cell viability decreased. F and ERK1/2 inhibitors antagonized extracellular-calcium-free-hypoxia/reoxygenation-induced ERK1/2 activation and suppressed cardiomyocytes damage. The ERK1/2 activator antagonized F's above effects. F had no effect on cardiomyocyte cAMP content or PKA and Egr-1 expression. Altogether, ERK activation in extracellular-calcium-containing and extracellular-calcium-free hypoxia/reoxygenation leads to cardiomyocytes damage. F may ameliorate cardiomyocytes hypoxia/reoxygenation injury by regulating the extracellular-calcium-dependent PKC/ERK1/2/Egr-1 pathway and through the extracellular-calcium-independent ERK1/2 activation independently of the cAMP/PKA pathway or Egr-1 overexpression. © 2013 Yanmei Zhang et al.

Bibliographic Details

Zhang, Yanmei; Chen, Gaoyong; Zhong, Shuping; Zheng, Fuchun; Gao, Fenfei; Chen, Yicun; Huang, Zhanqin; Cai, Wenfeng; Li, Weiqiu; Liu, Xingping; Zheng, Yanshan; Xu, Han; Shi, Ganggang

Hindawi Limited

Biochemistry, Genetics and Molecular Biology

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