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摘要
N-n-butyl haloperidol iodide ( F 2) 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 2 ameliorates cardiomyocytes hypoxia/reoxygenation injury through the extracellularcalcium- 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 2 downregulated hypoxia/reoxygenation-induced elevation of p-PKC.., p-ERK1/2, and Egr1 expression and inhibited cardiomyocytes damage. The ERK1/2 and PKC.. activators antagonized F 2 ' s effects. In extracellularcalcium- free-hypoxia/reoxygenation cardiomyocytes, ERK1/2 was activated, LDH and cTnI leakage increased, and cell viability decreased. F 2 and ERK1/2 inhibitors antagonized extracellular-calcium-free-hypoxia/reoxygenation-induced ERK1/2 activation and suppressed cardiomyocytes damage. The ERK1/2 activator antagonized F 2 ' s above effects. F 2 had no effect on cardiomyocyte cAMP content or PKA and Egr-1 expression. Altogether, ERK activation in extracellular-calcium-containing and extracellularcalcium- free hypoxia/reoxygenation leads to cardiomyocytes damage. F 2 may ameliorate cardiomyocytes hypoxia/reoxygenation injury by regulating the extracellular-calcium-dependent PKC.. /ERK1/2/Egr-1 pathway and through the extracellular-calciumindependent ERK1/2 activation independently of the cAMP/PKA pathway or Egr-1 overexpression.
- 出版日期2013
- 单位汕头大学
