title: The Protective Effect of INH2BP, a Novel PARP Inhibitor 5-Iodo-6-Amino-1,2-Benzopyrone, Against Hydrogen Peroxide-Induced Apoptosis Through ERK and p38 MAPK in H9c2 Cells.
abstract: INH2BP (5-iodo-6-amino-1,2-benzopyrone), a poly-ADP ribose polymerase inhibitor, has been shown to possess anti-cancer, anti-viral, and anti-inflammation properties. The aim of this study was to investigate the protective effect of INH2BP against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells. While the treatment of H9c2 cardiomyoblasts cells with hydrogen peroxide (H2O2) caused a loss of cell viability and an increase in the number of apoptotic cells, INH2BP significantly protected the cells against H2O2-induced cell death without any cytotoxicity. Our data also shows that INH2BP significantly scavenged intracellular reactive oxygen species (ROS), and markedly enhanced the expression of antioxidant enzymes such as Mn-SOD (superoxide) and Cu/Zn-SOD, and heme oxygenase-1, which was accompanied by the concomitant activation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in H9c2 cells. The effects of INH2BP on ERK1/2 and p38 MAPK phosphorylation were abrogated by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. In addition, inhibition of ERK1/2 and p38 MAPK by these inhibitors significantly attenuated INH2BP-mediated H9c2 viability as well as cleaved caspases-3, Bax, and Bcl-2 activation. Taken together, these results demonstrate that INH2BP prevents H2O2-induced apoptosis in H9c2 cells by reducing the production of intracellular ROS, regulating apoptotic-related proteins, and the activation of the ERK1/2 and p38 MAPK.
authors.affiliation: Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Oun-Cheol
authors.initials: OC
authors.lastname: Back
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Jang
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Lee
authors.forename: Dae-Eun
authors.initials: DE
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: In Sik
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000201:enzymology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D003374:Coumarins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020011:Protective Agents; D017382:Reactive Oxygen Species; C071383:5-iodo-6-amino-1,2-benzopyrone; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases