Endothelin-1 is a potent survival factor for c-Myc-dependent apoptosis.
Endothelin-1 is a potent survival factor for c-Myc-dependent apoptosis.
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DOI：
10.1210/mend.12.2.0064
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发表时间：
1998-02
影响因子：
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通讯作者：
M. Shichiri;J. Sedivy;F. Marumo;Y. Hirata
中科院分区：
文献类型：
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作者：
M. Shichiri;J. Sedivy;F. Marumo;Y. Hirata
许多脊椎动物细胞对凋亡刺激具有抗性，其种类和所涉及的机制尚不完全清楚。内皮素-1是一种内皮源性的血管活性肽，其介导许多生理功能，如血管收缩和细胞增殖。c-Myc表达失调诱导血清剥夺成纤维细胞凋亡使用一组具有不同c-myc表达水平的同基因成纤维细胞系，我们证明低剂量的内皮素-1保护成纤维细胞免受血清剥夺诱导的凋亡，这是通过c-Myc依赖性过程发生的。内皮素-1诱导的细胞存活由ET（A）受体介导，与内皮素-1诱导细胞增殖的能力无关。通过抑制丝裂原活化蛋白激酶途径，内皮素-1的存活功能被废除。这些结果表明内皮素-1作为c-Myc依赖性细胞凋亡的有效存活因子的作用是迄今为止未被认识到的，这是一个由ET（A）受体和促分裂原活化蛋白激酶途径介导的过程。
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 ET(A) 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 ET(A) receptor and the mitogen-activated protein kinase pathway.