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Endothelin-1 Is a Potent Survival Factor for c-Myc-Dependent Apoptosis

1998; Oxford University Press; Volume: 12; Issue: 2 Linguagem: Inglês

10.1210/mend.12.2.0064

1944-9917

Masayoshi Shichiri, John M. Sedivy, Fumiaki Marumo, Yukio Hirata,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Abstract Many vertebrate cells are resistant to apoptotic stimuli, whose variety and the mechanisms involved are not fully understood. Endothelin-1 is an endothelium-derived vasoactive peptide that mediates many physiological functions, such as vasoconstriction and cell proliferation. Deregulated expression of c-Myc induces apoptosis in serum-deprived fibroblasts. Using a panel of isogenic fibroblast cell lines with differential c-myc expression levels, we demonstrate that low doses of endothelin-1 protect fibroblasts against serum deprivation-induced apoptosis, which occurs through a c-Myc-dependent process. The endothelin-1-induced cell survival was mediated by the ETA receptor and was not linked to the ability of endothelin-1 to induce cell proliferation. The survival function of endothelin-1 was abrogated by inhibiting the mitogen-activated protein kinase pathway. These results demonstrate a hitherto unappreciated role of endothelin-1 as a potent survival factor for c-Myc-dependent apoptosis, a process mediated by the ETA receptor and the mitogen-activated protein kinase pathway.