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首页> 外文期刊>Journal of biochemical and molecular toxicology >Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells.
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Effect of mitochondrial dysfunction and oxidative stress on endogenous levels of coenzyme Q(10) in human cells.

机译:线粒体功能障碍和氧化应激对人体细胞内源性辅酶Q(10)的影响。

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Little is known about the regulation of endogenous CoQ(10) levels in response to mitochondrial dysfunction or oxidative stress although exogenous CoQ(10) has been extensively used in humans. In this study, we first demonstrated that acute treatment of antimycin A, an inhibitor of mitochondrial complex III, and the absence of mitochondrial DNA suppressed CoQ(10) levels in human 143B cells. Because these two conditions also enhanced formation of reactive oxygen species (ROS), we further investigated whether oxidative stress or mitochondrial dysfunction primarily contributed to the decrease of CoQ(10) levels. Results showed that H(2)O(2) augmented CoQ(10) levels, but carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a chemical uncoupler, decreased CoQ(10) levels in 143B cells. However, H(2)O(2) and FCCP both increased mRNA levels of multiple COQ genes for biosynthesis of CoQ(10) . Our findings suggest that ROS induced CoQ(10) biosynthesis, whereas mitochondrial energy deficiency caused secondary suppression of CoQ(10) levels possibly due to impaired import of COQ proteins into mitochondria.
机译:尽管外源性CoQ(10)已广泛用于人类,但对响应线粒体功能障碍或氧化应激的内源性CoQ(10)水平的调节知之甚少。在这项研究中,我们首先证明了抗霉素A(线粒体复合物III的抑制剂)的急性治疗和线粒体DNA的缺乏抑制了人143B细胞中的CoQ(10)水平。因为这两个条件还增强了活性氧(ROS)的形成,所以我们进一步研究了氧化应激或线粒体功能障碍是否主要是导致CoQ(10)水平降低的原因。结果表明,H(2)O(2)增加了CoQ(10)的水平,但是羰基氰化物-对-三氟甲氧基苯基hydr(FCCP),一种化学解偶联剂,降低了143B细胞中的CoQ(10)的水平。但是,H(2)O(2)和FCCP都增加了生物合成CoQ(10)的多个COQ基因的mRNA水平。我们的研究结果表明,ROS诱导了CoQ(10)的生物合成,而线粒体能量缺乏导致了CoQ(10)水平的二次抑制,这可能是由于COQ蛋白导入线粒体的能力受损所致。

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