Title: PI3K/Akt signal pathway inhibits ischemia and hypoxia-induced myocardial apoptosis in rats
Abstract:Objective To investigate the role and mechanisms of the PI3K/Akt signal pathway in the apoptosis of rat cardiomyocytes after ischemia and hypoxia due to severe burn injury.Methods Burn models of full-...Objective To investigate the role and mechanisms of the PI3K/Akt signal pathway in the apoptosis of rat cardiomyocytes after ischemia and hypoxia due to severe burn injury.Methods Burn models of full-thick 30%TBSA burn injury were established by scalding rat back in hot water.The activation of the PI3K/Akt signal pathway was observed by Western blotting,and myocardial apoptosis was assessed by TUNEL.Cultured rat cardiomyocytes under ischemic/hypoxic conditions were divided into the control group,the ischemia and hypoxia group,and the LY294002 or IGF-1 treatment group.The apoptosis of cardiomyocytes were assessed by ELISA.The caspase-3 activity was measured by DEVD fluorescence.The transcriptional activity of p53,Bax was assessed by RT-PCR.Results After severe burn,PI3K and pAkt expressions increased gradually in the rat myocardial tissue,and reached a peak at 3 h postburn.At 3 h postburn,the apoptosis increased significantly in rats.When the PI3K/Akt pathway was specifically inhibited by LY294002,the myocardial apoptosis increased significantly in the burn group as compared with the control group(P0.05).Cultured cardiomyocytes after ischemia and hypoxia showed the following changes:increased apoptosis,gradually enhanced caspase-3 activity,gradually increased p53 and Bax mRNA expressions.Compared with the ischemia and hypoxia group,blockade of the PI3K/Akt pathway with LY294002 increased the number of apoptotic cardiomyo-cytes,caspase-3 activity,and p53 and Bax mRNA expression significantly(P0.05).After activation of the PI3K/Akt pathway with IGF-1,caspase-3 activity decreased significantly(P0.05),as compared with the ischemia and hypoxia group.Conclusion The PI3K/Akt signal pathway plays anti-apoptotic role in ischemic/hypoxic cardiomyocytes.PI3K/Akt pathway regulating p53 and Bax expression is probably the mechanism of anti-apoptosis,which can suppress the activity of caspase-3 and decrease the number of apoptotic cardiomyocytes.Read More
Publication Year: 2009
Publication Date: 2009-01-01
Language: en
Type: article
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