Cyclic AMP delays neutrophil apoptosis via stabilization of Mcl-1
Cyclic AMP delays neutrophil apoptosis via stabilization of Mcl-1
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DOI：
10.1016/j.febslet.2006.07.034
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发表时间：
2006-08-21
期刊：
影响因子：
3.5
通讯作者：
Kitagawa, Seiichi
中科院分区：
文献类型：
--
作者：
Kato, Takayuki;Kutsuna, Haruo;Kitagawa, Seiichi
人中性粒细胞发生自发性凋亡，伴随Mcl-1降解，而不是其他抗凋亡分子（cIAP 1，cIAP 2，A1，生存素和Bcl-2）。自发性中性粒细胞凋亡和Mcl-1降解可被cAMP激动剂（二丁酰cAMP和前列腺素E-1）阻止，cAMP激动剂对中性粒细胞的作用对蛋白质合成抑制剂放线菌酮具有高度抗性，尽管cAMP激动剂可诱导Mcl-1 mRNA表达轻微增加。蛋白酶体抑制剂（epoxomicin和lactacystin）也防止自发性中性粒细胞凋亡和Mcl-1降解到与cAMP激动剂相同的程度，cAMP激动剂和蛋白酶体抑制剂的组合没有获得累加效应。这些发现表明，cAMP激动剂，如蛋白酶体抑制剂，延迟中性粒细胞凋亡主要是通过稳定的Mcl-1。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Human neutrophils underwent spontaneous apoptosis, which was accompanied by degradation of Mcl-1, but not other anti-apoptotic molecules (cIAP1, cIAP2, A1, survivin and Bcl-2). Spontaneous neutrophil apoptosis and Mcl-1 degradation were prevented by cyclic AMP (CAMP) agonists (dibutyryl cAMP and prostaglandin E-1,), and the effects of cAMP agonists on neutrophils were highly resistant to cycloheximide, a protein synthesis inhibitor, although slight increase in Mcl-1 mRNA expression was induced by cAMP agonists. Proteasome inhibitors (epoxomicin and lactacystin) also prevented spontaneous neutrophil apoptosis and Mcl-1 degradation to the same extent as cAMP agonists, and no additive effect was obtained by combination of cAMP agonists and proteasome inhibitors. These findings suggest that cAMP agonists, like proteasome inhibitors, delay neutrophil apoptosis primarily via stabilization of Mcl-1. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.