p38 MAPK-Pim-3 signal pathway may be involved in cardiomyocyte anoxia preconditioning against anoxia/reoxygenation injury

AIM:To investigate the role of mitogen-activated protein kinases(MAPKs)pathways and the molecular mechanism by which the proto-oncogene Pim-3 protects cardiomyocyte against anoxia/reoxygenation(A/R)injury.METHODS:The primarily cultured neonatal rat ventricular cardiomyocytes were randomly divided into 4 groups:control group;A/R group;APC+A/R group;SB203850,U0126 or SP600125+APC+A/R group.The cells were pre-incubated with U0126(ERK1/2 inhibitor),SP600125(SAPK/JNK inhibitor),or SB203850(p38 MAPK inhibitor)at concentration of 10 μmol/L for 30 min before the APC.The activities of p38 MAPK,JNK and ERK1/2 were detected by Western blotting.The viability of cardiomyocytes was assayed by MTT and the apoptosis of cardiomyocyte was detected by TUNEL.RESULTS:U0126,SB203850,and SP600125 abolished the increased expression of ERK1/2,p38-MAPK,and JNK proteins induced by APC+A/R or A/R,respectively.The expression level of Pim-3 protein significantly decreased when the p38 MAPK signal pathway was inhibited.Meanwhile,the activity of LDH and the apoptosis index increased,and the viability of cardiomyocytes decreased.CONCLUSION:Pim-3 expression through a p38 MAPK signaling pathway may protect cardiomyocytes from A/R injury.