Activation of the cAMP cascade in human fibroblast cultures rescues the activity of oxidatively damaged complex I

Activation of the cAMP cascade in human fibroblast cultures rescues the activity of oxidatively damaged complex I
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DOI:
10.1016/j.freeradbiomed.2011.11.030
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发表时间:
2012-02-15
影响因子:
7.4
通讯作者:
Papa, Sergio
Papa, Sergio
中科院分区:
医学1区
文献类型:
--
作者:
De Rasmo, Domenico;Signorile, Anna;Papa, Sergio

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研究cAMP/ pka依赖性磷酸化与线粒体呼吸链复合体I亚基氧化损伤之间的关系。研究表明,在成纤维细胞培养中,pka介导的复合物I的NDUFS4亚基磷酸化恢复了氧化损伤复合物的活性。有证据表明,这种作用是由组装复合物中羰基化NDUFS4亚基与新合成亚基的磷酸化依赖交换介导的。这些结果表明β -肾上腺素能受体激动剂在预防/逆转线粒体呼吸系统氧化应激的有害影响方面具有潜在的用途。(C) 2011爱思唯尔公司版权所有。
A study of the relationship between cAMP/PKA-dependent phosphorylation and oxidative damage of subunits of complex I of the mitochondrial respiratory chain is presented. It is shown that, in fibroblast cultures, PKA-mediated phosphorylation of the NDUFS4 subunit of complex I rescues the activity of the oxidatively damaged complex. Evidence is presented showing that this effect is mediated by phosphorylation-dependent exchange of carbonylated NDUFS4 subunit in the assembled complex with the de novo synthesized subunit. These results indicate a potential use for beta-adrenoceptor agonists in preventing/reversing the detrimental effects of oxidative stress in the mitochondrial respiratory system. (C) 2011 Elsevier Inc. All rights reserved.