Superoxide induces apoptosis in cardiomyocytes, but proliferation and expression of transforming growth factor-beta 1 in cardiac fibroblasts

Cardiomyocyte apoptosis and cardiac fibroblast proliferation are characteri stic features of failing myocardium. Here we investigated the effect of sup eroxide on the cell fate of cardiomyocytes and cardiac fibroblasts. Culture d rat cardiomyocytes or cardiac fibroblasts were treated with superoxide. I n response to superoxide stimulation cardiomyocytes under-went apoptosis as revealed by the increase in histone associated DNA fragmentation and posit ive to in situ nick end-labeling. In contrast, cardiac fibroblasts were sti mulated to proliferate as demonstrated by the increase in DNA synthesis det ected by [H-3]thymidine incorporation and in cell number. Additionally, Nor thern blot analysis showed that transforming growth factor-beta 1, a key fa ctor responsible for myocardial fibrosis, was upregulated in cardiac fibrob lasts in response to superoxide stimulation. These data suggest that supero xide can induce such divergent effects as apoptosis in cardiomyocytes and c ell growth in cardiac fibroblasts, indicating that it may be a potential fa ctor involved in the pathogenesis of heart failure. (C) 1999 Federation of European Biochemical Societies.