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EXPERIMENTAL STUDY

Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts

^a Gerontology Division, Department of Medicine, Beth Israel Deaconess Medical Center and the Division on Aging, Harvard Medical School, Boston, Massachusetts, USA

Manuscript received November 21, 2000; revised manuscript received July 11, 2001, accepted August 29, 2001.

^* Reprint requests and correspondence: Dr. Jeanne Y. Wei, Gerontology Division, RA-440, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215 USA
jwei{at}caregroup.harvard.edu

OBJECTIVES

This study was designed to test the hypothesis that cardiac myocytes have greater vulnerability to oxidative stress compared with cardiac fibroblasts.

BACKGROUND

The function of cardiac myocytes differs from that of fibroblasts in the heart, but differences in their response to oxidative stress have not been extensively studied.

METHODS

Cardiomyocytes and fibroblasts from F344 neonatal rat hearts were cultured and exposed to different concentrations of hydrogen peroxide (H₂O₂) and menadione (superoxide generator). The mitogen-activated protein kinase (MAPK) proteins were assayed after oxidative stress; cell death was determined by trypan blue staining and deoxyribonucleic acid (DNA) ladder electrophoresis.

RESULTS

The cardiac myocytes were significantly more vulnerable than the fibroblasts to oxidative damage, showing substantial DNA fragmentation and consistently poor cell survival after exposure to H₂O₂ (100 to 800 µM), while the cardiac fibroblasts demonstrated little or no DNA fragmentation, and superior cell survival rates both over time (from 1 to 72 h after 100 µM) and across increasing doses of H₂O₂ (100 to 800 µM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H₂O₂, but significantly more in cardiac fibroblasts. However, p38 MAPK and c-jun NH₂-terminal kinase were phosphorylated more in the cardiac myocytes compared to cardiac fibroblasts. This was also the case after exposure to menadione.

CONCLUSION

Taken together, these results suggest that oxidative stress causes greater injury and cell death in cardiac myocytes compared with cardiac fibroblasts. It is possible that the signaling differences via the MAPK family may partly mediate the observed differences in vulnerability and functional outcomes of the respective cell types.

Abbreviations and Acronyms   ANOVA = analysis of variance   DNA = deoxyribonucleic acid   ERK = extracellular signal-regulated kinases   H2O2 = hydrogen peroxide   JNK = c-jun NH2 terminal kinase   MAPK = mitogen-activated protein kinase   PBS = phosphate-buffered saline solution   PD-98059 = Parke-Davis compound 98059   SB-202190, 203580 = Smith Kline and Beecham 202190, 203580   SDS-PAGE = sodium dodecyl sulfate-polyacrylamide gel electrophoresis

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