Expressions of GRP78 and CHOP in endoplasmic reticulum stress of rat heart after aortic constriction and their relationship with cardiac myocyte apoptosis

Chinese Heart Journal(2010)

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Abstract
AIM: To study the expression of glucose-regulated protein 78(GRP78) and C/EBP homologous protein(CHOP) in rat heart after aortic constriction and their relationship with cardiac myocyte apoptosis.METHODS: Healthy male Sprague Dawley rats were randomly divided into transverse aortic constriction(TAC) group and sham group.The rats in TAC group received abdominal TAC.Blood pressures were measured on the 3rd,7th,14th and 28th day after surgery.Western blot was used to assess the protein level of GRP78 and CHOP and TUNEL was used to detect the cardiac myocyte apoptosis.RESULTS: Compared with those in sham group,the mean arterial pressure(MAP) of rats in TAC group increased significantly on the third day after TAC and increased progressively during the experiment(P0.05).On day 3 after TAC,the protein level of GRP78 in TAC group increased compared with that in control group(P0.05),but its expression was lower than that on days 7,14 and 28(P0.05).On day 7 after TAC,the protein level in the TAC group was the highest and although it decreased on days 14 and 28,high levels sustained compared with sham group(P0.05).After TAC,the protein levels of CHOP in TAC groups increased progressively and,except on day 3(P0.05),they were higher than those in sham group(P0.05).On day 7 after surgery,cardiac myocyte apoptosis in both TAC group and sham group could be detected by TUNEL,and the incidence of cardiac myocyte apoptosis increased progressively.The incidence of cardiac myocyte apoptosis in TAC group on day 28 after TAC was(30.23±0.17)%,which was the highest.Correlation analysis indicated a negative correlation between MAP and GRP78 protein expression in TAC group from day 7 after TAC(r=-0.882,P0.01) and a positive correlation between the MAP and CHOP protein expression(r=0.933,P0.01).The analysis also indicated a negative correlation between CHOP protein expression and GRP78 protein expression(r=-0.980,P0.01),and a positive correlation between CHOP protein expression and the incidence of cardiac myocyte apoptosis(r=0.997,P0.01).CONCLUSION: TAC-caused hypertension induces endoplasmic reticulum stress.At the early stage of hypertension,the expression of GRP78 has the highest status.Although prolonged endoplasmic reticulum stress activated by hypertension induces a significant upregulation in CHOP,CHOP may participate in myocyte apoptosis in hypertension and cause the regulatory disequilibrium of endoplasmic reticulum stress.
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Key words
apoptosis,hypertension,myocardial cell,GRP78,CHOP,endoplasmic reticulum stress,rat
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