Suppression of coenzyme Q10 levels and the induction of multiple PDSS and COQ genes in human cells following oligomycin treatment

被引:11
作者
Yen, H. -C. [1 ]
Liu, C. -C. [1 ]
Kan, C. -C. [1 ]
Chen, C. -S. [1 ]
Wei, H. -R. [1 ]
机构
[1] Chang Gung Univ, Dept & Grad Inst Med Biotechnol & Lab Sci, Coll Med, Taoyuan 333, Taiwan
关键词
ATP synthase; reactive oxygen species; COQ genes; PGC-1alpha; N-acetylcysteine; Q BIOSYNTHESIS; UP-REGULATION; ATP SYNTHASE; MITOCHONDRIA; PGC-1-ALPHA; DEFICIENCY; PROTEINS; STRESS; YEAST;
D O I
10.3109/10715762.2014.936865
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endogenous coenzyme Q(10) (CoQ(10)) is a lipid-soluble antioxidant and essential for the electron transport chain. We previously demonstrated that hydrogen peroxide enhanced CoQ(10) levels, whereas disruption of mitochondrial membrane potential by a chemical uncoupler suppressed CoQ(10) levels, in human 143B cells. In this study, we investigated how CoQ(10) levels and expression of two PDSS and eight COQ genes were affected by oligomycin, which inhibited ATP synthesis at Complex V without uncoupling the mitochondria. We confirmed that oligomycin increased the production of reactive oxygen species (ROS) and decreased mitochondria-dependent ATP production in 143B cells. We also demonstrated that CoQ(10) levels were decreased by oligomycin after 42 or 48 h of treatment, but not at earlier time points. Expression of PDSS2 and COQ2-COQ9 were up-regulated after 18-hour oligomycin treatment, and the expression of PPARGC1A (PGC1-1 alpha) elevated concurrently. Knockdown of PPARGC1A down-regulated the basal mRNA levels of PDSS2 and five COQ genes and suppressed the induction of COQ8 and COQ9 genes by oligomycin, but did not affect CoQ(10) levels under these conditions. N-acetylcysteine suppressed the augmentation of ROS levels and the enhanced expression of COQ2, COQ4, COQ7, and COQ9 induced by oligomycin, but did not modulate the changes in CoQ(10) levels. These results suggested that the condition of mitochondrial dysfunction induced by oligomycin decreased CoQ(10) levels independent of oxidative stress. Up-regulation of PDSS2 and several COQ genes by oligomycin might be regulated by multiple mechanisms, including the signaling pathways mediated by PGC-1 alpha and ROS, but it would not restore CoQ(10) levels.
引用
收藏
页码:1125 / 1134
页数:10
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