Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts

OBJECTIVES This study was designed to test the hypothesis that cardiac myoc ytes have greater vulnerability to oxidative stress compared with cardiac f ibroblasts. BACKGROUND The function of cardiac myocytes differs from that of fibroblast s in the heart, but differences in their response to oxidative stress have not been extensively studied. METHODS Cardiomyocytes and fibroblasts from F344 neonatal rat he-arts were cultured and exposed to different concentrations of hydrogen peroxide (H2O2 ) and menadione (superoxide generator). The mitogen-activated protein kinas e (MAPK) proteins were assayed after oxidative stress; cell death was deter mined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electr ophoresis. RESULTS The cardiac myocytes were significantly more vulnerable than the fi broblasts to oxidative damage, showing substantial DNA fragmentation and co nsistently poor cell survival after exposure to H2O2 (100 to 800 muM), whil e the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 muM) and across increasing doses of H2O2 (100 to 800 muM). The p42/44 extracellu lar signal-regulated kinases were phosphorylated in both cell types after e xposure to H2O2, but significantly more in cardiac fibroblasts. However, p3 8 MAPK and c-jun NH2-terminal kinase were phosphorylated more in the cardia c myocytes compared to cardiac fibroblasts. This was also the case after ex posure to menadione. CONCLUSION Taken together, these results suggest that oxidative stress caus es greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK fam ily may partly mediate the observed differences in Vulnerability and functi onal outcomes of the respective cell types. (J Am Coll Cardiol 2001;38:2055 -62) (C) 2001 by the American College of Cardiology.