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.
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.
Authors: Sven Y Surikow; Thanh H Nguyen; Irene Stafford; Matthew Chapman; Sujith Chacko; Kuljit Singh; Giovanni Licari; Betty Raman; Darren J Kelly; Yuan Zhang; Mark T Waddingham; Doan T Ngo; Alexander P Bate; Su Jen Chua; Michael P Frenneaux; John D Horowitz Journal: JACC Basic Transl Sci Date: 2018-04-18