Acrolein inhibits respiration in isolated brain mitochondria
Acrolein inhibits respiration in isolated brain mitochondria
复制标题
DOI：
10.1016/s0925-4439(00)00093-4
复制
发表时间：
2001-02-14
影响因子：
6.2
通讯作者：
Montine, TJ
中科院分区：
文献类型：
--
作者：
Picklo, MJ;Montine, TJ
在一些神经退行性疾病中，脂质过氧化在脑病变区域升高。丙烯醛（2-propenal）是脂质过氧化的主要细胞毒性产物，其内聚到神经元蛋白已在阿尔茨海默病患者的病变脑区得到证实。线粒体异常与几种神经退行性疾病有关，线粒体是体内烯醛内收的靶标。我们检查了丙烯醛对与线粒体参与神经退行性疾病相关的多个终点的影响。丙烯醛抑制状态3呼吸，IC50约为。0.4 μ mol/mg蛋白质；然而，复合物I-V的活性没有降低。这种抑制作用被谷胱甘肽和n -乙酰半胱氨酸所阻止。丙烯醛不改变线粒体钙转运蛋白活性或诱导细胞色素c释放。这些研究表明丙烯醛是脑线粒体呼吸的有效抑制剂。(C) 2001 Elsevier Science B.V.版权所有
Lipid peroxidation is elevated in diseased regions of brain in several neurodegenerative diseases. Acrolein (2-propenal) is a major cytotoxic product of lipid peroxidation and its adduction to neuronal proteins has been demonstrated in diseased brain regions from patients with Alzheimer's disease. Mitochondrial abnormalities are implicated in several neurodegenerative disorders, and mitochondria are targets of alkenal adduction in vivo. We examined the effects of acrolein upon multiple endpoints associated with the mitochondrial involvement in neurodegenerative disease. Acrolein inhibited state 3 respiration with an IC50 of approx. 0.4 mu mol/mg protein; however, there was no reduction in activity of complexes I-V. This inhibition was prevented by glutathione and N-acetylcysteine. Acrolein did not alter mitochondrial calcium transporter activity or induce cytochrome c release. These studies indicate that acrolein is a potent inhibitor of brain mitochondrial respiration. (C) 2001 Elsevier Science B.V. All rights reserved.