Superoxide induces apoptosis in cardiomyocytes, but proliferation and expression of transforming growth factor-beta1 in cardiac fibroblasts.
Cardiomyocyte apoptosis and cardiac fibroblast proliferation are characteristic features of failing myocardium. Here we investigated the effect of superoxide on the cell fate of cardiomyocytes and cardiac fibroblasts. Cultured rat cardiomyocytes or cardiac fibroblasts were treated with superoxide. In response to superoxide stimulation cardiomyocytes underwent apoptosis as revealed by the increase in histone associated DNA fragmentation and positive to in situ nick end-labeling. In contrast, cardiac fibroblasts were stimulated to proliferate as demonstrated by the increase in DNA synthesis detected by [3H]thymidine incorporation and in cell number. Additionally, Northern blot analysis showed that transforming growth factor-beta1, a key factor responsible for myocardial fibrosis, was upregulated in cardiac fibroblasts in response to superoxide stimulation. These data suggest that superoxide can induce such divergent effects as apoptosis in cardiomyocytes and cell growth in cardiac fibroblasts, indicating that it may be a potential factor involved in the pathogenesis of heart failure.
Li
P F
PF
Department of Cardiology, Franz Volhard Clinic, Humboldt University Berlin, and Max-Delbrück-Center for Molecular Medicine, Germany.
Dietz
R
R
von Harsdorf
R
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006861:Hydrogen Peroxide / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
D000199:Actins; D016212:Transforming Growth Factor beta; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase