Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE) -: Role of HNE adduct formation with the enzyme subunits
Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal (HNE) -: Role of HNE adduct formation with the enzyme subunits
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DOI：
10.1016/s0304-4165(98)00002-6
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发表时间：
1998-05-08
影响因子：
3
通讯作者：
Henderson, GI
中科院分区：
文献类型：
--
作者：
Chen, JJ;Schenker, S;Henderson, GI
研究了脂质过氧化产物4-羟基壬烯醛（HNE）在线粒体细胞色素c氧化酶（考克斯）氧化损伤中的作用。用叔丁基过氧化氢（t-BHP）诱导雄性Sprague-Dawley大鼠肝线粒体氧化应激。考克斯酶活性受到抑制，同时线粒体内源性HNE水平增加。线粒体孵育50-150 μ M HNE后，考克斯活性也受到抑制。阻断HNE降解增强了HNE和t-BHP诱导的氧化应激对考克斯的抑制作用，后者伴随着内源性HNE产生的同时增加。另一方面，HNE对考克斯的抑制作用通过增强HNE与还原型谷胱甘肽（GSH）的结合而增强HNE降解而显著降低。将纯化的考克斯与10-400 μ M HNE孵育，导致与考克斯的特定亚基形成HNE加合物，与酶活性的抑制相关。这些数据表明，HNE可能通过与酶形成加合物来抑制线粒体考克斯，这可能是氧化应激引起线粒体损伤的一种机制。这些发现也说明了GSH在保护线粒体免受HNE的有害影响方面的作用。(C)1998年Elsevier Science B.V.
The role of 4-hydroxynonenal (HNE), a major lipid peroxidation product in oxidative damage to mitochondrial cytochrome c oxidase (COX) was examined. Oxidative stress was induced in mitochondria isolated from livers of male Sprague-Dawley rats by tert-butylhydroperoxide (t-BHP). COX activity was inhibited, with a concommitant increase in endogenous HNE level in mitochondria. COX activity was also inhibited following incubation of mitochondria 50-150 mu M HNE. Blocking HNE degradation intensified COX inhibition by HNE and by t-BHP-induced oxidative stress, the latter accompanied by a simultaneous increase in endogenous HNE production. On the other hand, COX inhibition by HNE was markedly reduced by potentiating HNE degradation via enhancing conjugation of HNE with reduced glutathione (GSH). Incubation of purified COX with 10-400 mu M HNE resulted in HNE adduct formation with specific subunits of COX, correlated with inhibition of the enzyme activity. These data suggest that HNE may inhibit mitochondrial COX by forming adducts with the enzyme, and that this could be one mechanism underlying mitochondrial damage caused by oxidative stress. The findings also illustrate a role for GSH in protecting mitochondria from the deleterious effects of HNE. (C) 1998 Elsevier Science B.V.