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Oxidative modifications of cardiac mitochondria and inhibition of cytochrome c oxidase activity by 4-hydroxynonenal.
Redox Report ( IF 5.2 ) Pub Date : 2007-10-11 , DOI: 10.1179/135100007x200308
Peter Kaplan 1 , Zuzana Tatarkova , Peter Racay , Jan Lehotsky , Martina Pavlikova , Dusan Dobrota
Affiliation  

4-hydroxynonenal (HNE) is a highly toxic product of lipid peroxidation (LPO). Its role in the inhibition of cytochrome c oxidase activity and oxidative modifications of mitochondrial lipids and proteins were investigated. The exposure of mitochondria isolated from rat heart to HNE resulted in a time- and concentration-dependent inhibition of cytochrome c oxidase activity with an IC50 value of 8.3 +/- 1.0 microM. Immunoprecipitation-Western blot analysis showed the formation of HNE adducts with cytochrome c oxidase subunit I. The loss of cytochrome c oxidase activity was also accompanied by reduced thiol group content and increased HNE-lysine fluorescence. Furthermore, there was a marked increase in conjugated diene formation indicating LPO induction by HNE. Fluorescence measurements revealed the formation of bityrosines and increased surface hydrophobicity of HNE-treated mitochondrial membranes. Superoxide dismutase + catalase and the HO* radical scavenger mannitol partially prevented inhibition of cytochrome c oxidase activity and formation of bityrosines. These findings suggest that HNE induces formation of reactive oxygen species and its damaging effect on mitochondria involves both formation of HNE-protein adducts and oxidation of membrane lipids and proteins by free radicals.

中文翻译:

心脏线粒体的氧化修饰和4-羟基壬烯醛对细胞色素c氧化酶活性的抑制。

4-羟基壬烯醛(HNE)是脂质过氧化(LPO)的剧毒产物。研究了其在抑制细胞色素c氧化酶活性以及线粒体脂质和蛋白质的氧化修饰中的作用。从大鼠心脏分离的线粒体暴露于HNE会导致时间依赖性和浓度依赖性的细胞色素C氧化酶活性抑制,IC50值为8.3 +/- 1.0 microM。免疫沉淀-Western印迹分析显示,HNE加合物与细胞色素C氧化酶亚基I形成。细胞色素C氧化酶活性的丧失还伴随着巯基含量的减少和HNE-赖氨酸荧光的增加。此外,共轭二烯的形成显着增加,表明HNE诱导了LPO。荧光测量结果显示,在HNE处理的线粒体膜上形成了酪氨酸,并增加了表面疏水性。超氧化物歧化酶+过氧化氢酶和HO *自由基清除剂甘露醇可部分阻止细胞色素C氧化酶活性的抑制和双酪氨酸的形成。这些发现表明,HNE诱导了活性氧的形成,其对线粒体的破坏作用既涉及HNE蛋白加合物的形成,也涉及自由基对膜脂质和蛋白的氧化作用。
更新日期:2019-11-01
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