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首页> 外文期刊>Biochemistry >Suppression of Programmed Cell Death by Intracellular cAMP Is not Mediated by Expression of Genes Encoding an Inhibitor of Apoptosis
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Suppression of Programmed Cell Death by Intracellular cAMP Is not Mediated by Expression of Genes Encoding an Inhibitor of Apoptosis

机译：胞内cAMP抑制程序性细胞死亡并不由编码凋亡抑制剂的基因表达介导。

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The elevation of intracelular cAMP content is accompanied by expression of genes whose promoter contains a Ca~(2+)-cAMP responsive element. In vascular smooth muscle cells (VSMC), activation of cAMP signaling blocks apoptosis triggered by serum deprivation. in the present study we investigated the role of gene expression in the inhibition of apoptosis by cAMP. In VSMC transfected with E1A adenovirus, incubation in the absence of serum for 6 h led to 20-fold elevation of chromatin fragmentation and 10-fold activation of caspase-3 activity, these being employed as markers of apoptosis. Forskolin-induced activation of cAMP signaling was accompanied by 50% elevation of RNA synthesis and completely abolished the development of apoptosis during the initial 6 h inclubation in growth factor-free mediu. In 12 h apotosis inforskolin-treated vVSMC was slowly developed and after 24 h the content of chromatin fragments was 2-fold less than in control cells. Addition of actinomycin D and cycloheximide completely blocked RNA synthesis and deceased protein synthesis by 80%, respectively. Neither compound affected baseline apoptosis or its inhibition by forskolin. More than 70 newly phosphorylated proteins were observed by 2D-electrophoriesis of VSMC after incubation with forskolin for3 h; in 24 h the number of phosphoproteins triggered by forskolin was decreased by 2-3-fold. These results show that suppression of VSMC apoptosis under activtion of cAMP signaling is mediated via posttranslational modification of pre-existing intermediates of the apoptotic machinery rather than by de novo synthesis of inhibitors of programmed cell death.
机译：胞内cAMP含量的增加伴随着其启动子包含Ca〜（2 +）-cAMP响应元件的基因的表达。在血管平滑肌细胞（VSMC）中，cAMP信号的激活阻断了血清剥夺触发的凋亡。在本研究中，我们研究了基因表达在cAMP抑制细胞凋亡中的作用。在用E1A腺病毒转染的VSMC中，在无血清的条件下温育6小时会导致染色质碎片增加20倍，激活caspase-3活性增加10倍，这些被用作凋亡的标志物。 Forskolin诱导的cAMP信号传导激活伴随着50％的RNA合成升高，并在无生长因子的最初6小时内完全消除了细胞凋亡的发展。在12 h的凋亡过程中，用Inforskolin处理的vVSMC缓慢发育，并且在24 h后，染色质片段的含量比对照细胞少2倍。放线菌素D和环己酰亚胺的添加分别完全阻止了RNA合成和80％的蛋白质合成失败。两种化合物均不影响基线凋亡或其被毛喉素抑制。与毛喉素孵育3 h后，通过VSMC的2D电泳观察到70多个新的磷酸化蛋白。在24小时内，福司可林触发的磷蛋白数量减少了2-3倍。这些结果表明在cAMP信号激活下对VSMC凋亡的抑制作用是通过对凋亡机制预先存在的中间体进行翻译后修饰而不是通过程序性细胞死亡抑制剂的从头合成来实现的。

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