Differential vulnerability to oxidative stress in rat cardiac myocytes versus fibroblasts

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 (H₂₂) 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 H₂₂ (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 H₂₂ (100 to 800 μM). The p42/44 extracellular signal-regulated kinases were phosphorylated in both cell types after exposure to H₂₂, 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.