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Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells.
J Mol Cell Cardiol. 1998 Sep; 30(9):1789-801.JM

Abstract

The aim of this study was to test the hypothesis that oxidative stress induces apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen-activated protein kinase (MAPK) pathways is involved. Three forms of oxidative stress were utilized: the superoxide generator menadione; hydrogen peroxide; or simulated ischemia followed by reperfusion. Relatively low concentrations of menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA fragmentation and caspase activation, both markers for apoptotic cell death, and preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK pathways. In contrast, higher concentrations of menadione or H 2O2 caused less DNA fragmentation, more necrotic cell death and preferential activation of the extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did not induce DNA fragmentation or caspase activation and activated only the p38 MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation, caspase activation, necrotic cell death and activation of all three MAPK pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB-203580, respectively) had no effect on the extent of oxidative stress-induced DNA fragmentation or caspase activation. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of DNA fragmentation and caspase activation induced by oxidative stress. In conclusion, these data suggest that the JNK pathway plays an important role in signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells.

Authors+Show Affiliations

Department of Medicine, Harvard Medical School, Boston, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9769235

Citation

Turner, N A., et al. "Oxidative Stress Induces DNA Fragmentation and Caspase Activation Via the c-Jun NH2-terminal Kinase Pathway in H9c2 Cardiac Muscle Cells." Journal of Molecular and Cellular Cardiology, vol. 30, no. 9, 1998, pp. 1789-801.
Turner NA, Xia F, Azhar G, et al. Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J Mol Cell Cardiol. 1998;30(9):1789-801.
Turner, N. A., Xia, F., Azhar, G., Zhang, X., Liu, L., & Wei, J. Y. (1998). Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. Journal of Molecular and Cellular Cardiology, 30(9), 1789-801.
Turner NA, et al. Oxidative Stress Induces DNA Fragmentation and Caspase Activation Via the c-Jun NH2-terminal Kinase Pathway in H9c2 Cardiac Muscle Cells. J Mol Cell Cardiol. 1998;30(9):1789-801. PubMed PMID: 9769235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. AU - Turner,N A, AU - Xia,F, AU - Azhar,G, AU - Zhang,X, AU - Liu,L, AU - Wei,J Y, PY - 1998/10/14/pubmed PY - 1998/10/14/medline PY - 1998/10/14/entrez SP - 1789 EP - 801 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 30 IS - 9 N2 - The aim of this study was to test the hypothesis that oxidative stress induces apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen-activated protein kinase (MAPK) pathways is involved. Three forms of oxidative stress were utilized: the superoxide generator menadione; hydrogen peroxide; or simulated ischemia followed by reperfusion. Relatively low concentrations of menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA fragmentation and caspase activation, both markers for apoptotic cell death, and preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK pathways. In contrast, higher concentrations of menadione or H 2O2 caused less DNA fragmentation, more necrotic cell death and preferential activation of the extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did not induce DNA fragmentation or caspase activation and activated only the p38 MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation, caspase activation, necrotic cell death and activation of all three MAPK pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB-203580, respectively) had no effect on the extent of oxidative stress-induced DNA fragmentation or caspase activation. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of DNA fragmentation and caspase activation induced by oxidative stress. In conclusion, these data suggest that the JNK pathway plays an important role in signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells. SN - 0022-2828 UR - https://www.unboundmedicine.com/medline/citation/9769235/Oxidative_stress_induces_DNA_fragmentation_and_caspase_activation_via_the_c_Jun_NH2_terminal_kinase_pathway_in_H9c2_cardiac_muscle_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(98)90743-X DB - PRIME DP - Unbound Medicine ER -