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Effects of 3-aminobenzamide on expressions of poly(ADP ribose) polymerase and apoptosis inducing factor in cardiomyocytes of rats with acute myocardial infarction
作者姓名:ZHAO Yu-juan  WANG Jian-hua  FU Bing  MA Mu-xin  LI Bao-xin  HUANG Qi  YANG Bao-feng
作者单位:ZHAO Yu-juan,WANG Jian-hua,FU Bing,MA Mu-xin(Department of Cardiology, First Clinical Medical College, Harbin Medical University, Harbin,150001, China);LI Bao-xin,YANG Bao-feng(Pharmacological College, Harbin Medical University, Harbin 150086, China);HUANG Qi(Centre for Cellular Morphology, Harbin Medical University,Harbin 150086, China) 
基金项目:黑龙江省自然科学基金,黑龙江省自然科学基金,Post-doctoral Foundation of Heilongjiang Province,Department of Edacation of Heilongjiang Province 
摘    要:Background Poly(ADP-ribose) polymerase (PARP) plays an important role in cell survival and death. However, the mechanisms involved are not fully understood. Therefore, we investigated the effect of inhibition of PARP on acute myocardial infarction (AMI) at different time points in rats. Methods AMI was induced in rats by ligating the left anterior descending coronary artery. One group received 3-aminobenzamide (3-AB, a kind of PARP inhibitor) (30 mg/kg) by intraperitoneal injection. The changes of ultramicrostructure of cardiocytes in infarction region were noted, PARP cleavage was measured by Western blotting, and expressions of protein of PARP and apoptosis inducing factor (AIF) were measured by immunohistochemical staining after treatment with 3-AB for 2 hours, 4 hours, 6 hours, 1 week, 4 weeks and 8 weeks. Results Few damages to the ultramicrostructure of cardiocytes were observed after treatment with 3-AB. PARP cleavage was detected as early as 4 hours and markedly increased by 6 hours following AMI without 3-AB, but was not found until 6 hours following AMI treated with 3-AB. There were significant differences between 3-AB and AMI groups at the same time points. The expression of PARP was observed gradually increased, but that of AIF was suppressed for 6 hours after treatment of 3-AB, compared with AMI groups in positive cells at the same time points. There was significantly less cleavage of PARP and more PARP expression in 3-AB treated group compared with AMI and control groups at all matched time points. Conclusions Our results suggest that 3-AB inhibits degradation of PARP, increases the expression of PARP protein, and suppresses the expression of AIF protein. Inhibition of PARP activity may protect cardiocytes in rats with AMI and reduce apoptosis.

关 键 词:急性心肌梗死  凋亡诱导因子  保护心肌细胞  聚合酶  二磷酸腺苷  大鼠  核糖  PARP

Effects of 3-aminobenzamide on expressions of poly(ADP ribose) polymerase and apoptosis inducing factor in cardiomyocytes of rats with acute myocardial infarction
ZHAO Yu-juan,WANG Jian-hua,FU Bing,MA Mu-xin,LI Bao-xin,HUANG Qi,YANG Bao-feng.Effects of 3-aminobenzamide on expressions of poly(ADP ribose) polymerase and apoptosis inducing factor in cardiomyocytes of rats with acute myocardial infarction[J].Chinese Medical Journal,2009,122(11):1322-1327.
Authors:ZHAO Yu-juan  WANG Jian-hua  FU Bing  MA Mu-xin  LI Bao-xin  HUANG Qi  YANG Bao-feng
Abstract:Background Poly(ADP-dbose) polymerase (PARP) plays an important role in cell survival and death. However, the mechanisms involved are not fully understood. Therefore, we investigated the effect of inhibition of PARP on acute myocardial infarction (AMI) at different time points in rats.Methods AMI was induced in rats by ligating the left antedor descending coronary artery. One group received 3-aminobenzamide (3-AB, a kind of PARP inhibitor) (30 mg/kg) by intrapedtoneal injection. The changes of ultramicrostructure of cardiocytes in infarction region were noted, PARP cleavage was measured by Westem blotting,and expressions of protein of PARP and apoptosis inducing factor (AIF) were measured by immunohistochemical staining after treatment with 3-AB for 2 hours, 4 hours, 6 hours, 1 week, 4 weeks and 8 weeks. Results Few damages to the ultramicrostructure of cardiocytes were observed after treatment with 3-AB. PARP cleavage was detected as eady as 4 hours and markedly increased by 6 hours following AMI without 3-AB, but was not found until 6 hours following AMI treated with 3-AB. There were significant differences between 3-AB and AMI groups at the same time points. The expression of PARP was observed gradually increased, but that of AIF was suppressed for 6 hours after treatment of 3-AB, compared with AMI groups in positive cells at the same time points. There was significantly less cleavage of PARP and more PARP expression in 3-AB treated group compared with AMI and control groups at all matched time points.Conclusions Our results suggest that 3-AB inhibits degradation of PARE increases the expression of PARP protein,and suppresses the expression of AIF protein. Inhibition of PARP activity may protect cardiocytes in rats with AMI and reduce apoptosis.
Keywords:3-aminobenzamide  acute myocardial infarction  poly(ADP-ribose) polymerase  apoptosis inducing factor  DNA repair  apoptosis
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