Carbon monoxide inhibits apoptosis in vascular smooth muscle cells
Carbon monoxide inhibits apoptosis in vascular smooth muscle cells
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DOI：
10.1016/s0008-6363(02)00410-8
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发表时间：
2002-08-01
影响因子：
10.8
通讯作者：
Durante, W
中科院分区：
文献类型：
--
作者：
Liu, XM;Chapman, GB;Durante, W
目的：一氧化碳（CO）是由血管平滑肌细胞通过血红素加氧酶1降解血红素而产生的。由于平滑肌细胞凋亡与许多血管疾病有关，我们研究了CO是否调节血管平滑肌细胞凋亡。方法和结果：用细胞因子（白细胞介素-1 β，5 ng/ml;肿瘤坏死因子-α，20 ng/ml;干扰素-γ，200 U/ml）的组合处理培养的大鼠主动脉平滑肌细胞48 h刺激细胞凋亡，如DNA梯状化、膜联蛋白V结合和半胱天冬酶-3激活所示。然而，外源性一氧化碳的管理，抑制马槟榔碱介导的细胞凋亡。CO的抗凋亡作用部分依赖于可溶性鸟苷酸环化酶的活化，并与线粒体细胞色素c释放的抑制和p53表达的抑制有关。平滑肌细胞与细胞因子的孵育也导致血红素加氧酶-1蛋白在刺激24小时后显著增加。血红素加氧酶抑制剂，锌原卟啉-IX，或CO清除剂，血红蛋白，刺激细胞凋亡后24小时的细胞因子暴露。结论：这些结果表明，CO，无论是外源性或内源性来源于血红素加氧酶-1活性，抑制血管平滑肌细胞凋亡。CO阻断平滑肌细胞凋亡的能力可能在阻断血管损伤部位的病变形成中起重要作用。(C)2002 Elsevier Science B. V.保留所有权利。
Objective: Carbon monoxide (CO) is generated from vascular smooth muscle cells via the degradation of heme by the enzyme heme oxygenase-1. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, we investigated whether CO regulates apoptosis in vascular smooth muscle. Methods and Results: Treatment of cultured rat aortic smooth muscle cells with a combination of cytokines (interleukin-1beta, 5 ng/ml; tumor necrosis factor-alpha, 20 ng/ml; interferon-gamma, 200 U/ml) for 48 h stimulated apoptosis, as demonstrated by DNA laddering, annexin V binding, and caspase-3 activation. However, the exogenous administration of CO inhibited cytokine-mediated apoptosis. The antiapoptotic action of CO was partially dependent on the activation of soluble guanylate cyclase and was associated with the inhibition of mitochondrial cytochrome c release and with the suppression of p53 expression. Incubation of smooth muscle cells with the cytokines also resulted in a pronounced increase in heme oxygenase-1 protein after 24 h of stimulation. The addition of the heme oxygenase inhibitor, zinc protoporphyrin-IX, or the CO scavenger, hemoglobin, stimulated apoptosis following 24 h of cytokine exposure. Conclusions: These results demonstrate that CO, either administered exogenously or endogenously derived from heme oxygenase-1 activity, inhibits vascular smooth muscle cell apoptosis. The ability of CO to block smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury. (C) 2002 Elsevier Science B.V. All rights reserved.