Role of mitochondrial electron transport complex I in coenzyme Q1 reduction by intact pulmonary arterial endothelial cells and the effect of hyperoxia
Role of mitochondrial electron transport complex I in coenzyme Q1 reduction by intact pulmonary arterial endothelial cells and the effect of hyperoxia
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DOI：
10.1152/ajplung.00448.2006
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Bongard, Robert D.
中科院分区：
文献类型：
--
作者：
Merker, Marilyn P.;Audi, Said H.;Bongard, Robert D.
线粒体电子传递复合物I在完整肺动脉内皮细胞辅酶Q（1）还原中的作用及高氧的影响美国生理学杂志肺细胞分子生理学293：L 809-L 819，2007年。首次发表于2007年6月29日; doi：10.1152/ajplung.00448.2006。- 目的是确定完整的常氧和高氧暴露（95%O-2 48 h）培养的牛肺动脉内皮细胞对辅酶Q（10）同系物辅酶Q（1）（CoQ（1））氧化还原状态的影响。当辅酶Q（1）（50 μ M）与细胞孵育30分钟时，其在培养基中的浓度随时间下降，在常氧条件下达到的水平低于高氧暴露的细胞。辅酶Q（1）浓度的降低与辅酶Q（1）氢醌（CoQ（1）H（2））的产生有关，其中在常氧条件下产生的CoQ（1）H（2）是高氧条件下的3.4倍（分别为8.2 +/- 0.3和2.4 +/- 0.4 μ M，平均值+/- SE）。高氧暴露细胞的最大辅酶Q1减少率，使用细胞膜不渗透的氧化还原指示剂铁氰化钾测量，约为含氧量正常的细胞的一半（11.4和24.1 nmol . min（-1）。mg（-1）细胞蛋白）。线粒体电子传递复合物I抑制剂鱼藤酮使常氧细胞中辅酶Q（1）的还原率降低了85%，使高氧暴露细胞中辅酶Q（1）的还原率降低了44%。NAD（P）H：醌氧化还原酶1（NQO（1））抑制剂对辅酶Q（1）还原几乎没有抑制作用。完整的细胞耗氧率和复合物I的活动，富甲油馏分也低于高氧暴露比常氧细胞。这意味着完整的肺内皮细胞通过复合物I介导的还原为辅酶Q（1）H（2）（出现在细胞外介质中）影响辅酶Q（1）的氧化还原状态，高氧暴露通过抑制复合物I活性降低了整体辅酶Q（1）还原能力。
Role of mitochondrial electron transport complex I in coenzyme Q(1) reduction by intact pulmonary arterial endothelial cells and the effect of hyperoxia. Am J Physiol Lung Cell Mol Physiol 293: L809-L819, 2007. First published June 29, 2007; doi:10.1152/ajplung.00448.2006. - The objective was to determine the impact of intact normoxic and hyperoxia-exposed ( 95% O-2 for 48 h) bovine pulmonary arterial endothelial cells in culture on the redox status of the coenzyme Q(10) homolog coenzyme Q(1) ( CoQ(1)). When CoQ(1) ( 50 mu M) was incubated with the cells for 30 min, its concentration in the medium decreased over time, reaching a lower level for normoxic than hyperoxia-exposed cells. The decreases in CoQ(1) concentration were associated with generation of CoQ(1) hydroquinone ( CoQ(1)H(2)), wherein 3.4 times more CoQ(1)H(2) was produced in the normoxic than hyperoxia-exposed cell medium ( 8.2 +/- 0.3 and 2.4 +/- 0.4 mu M, means +/- SE, respectively) after 30 min. The maximum CoQ1 reduction rate for the hyperoxia-exposed cells, measured using the cell membrane-impermeant redox indicator potassium ferricyanide, was about one-half that of normoxic cells ( 11.4 and 24.1 nmol . min(-1) . mg(-1) cell protein, respectively). The mitochondrial electron transport complex I inhibitor rotenone decreased the CoQ(1) reduction rate by 85% in the normoxic cells and 44% in the hyperoxia-exposed cells. There was little or no inhibitory effect of NAD( P) H: quinone oxidoreductase 1 ( NQO(1)) inhibitors on CoQ(1) reduction. Intact cell oxygen consumption rates and complex I activities in mitochondria-enriched fractions were also lower for hyperoxia-exposed than normoxic cells. The implication is that intact pulmonary endothelial cells influence the redox status of CoQ(1) via complex I-mediated reduction to CoQ(1)H(2), which appears in the extracellular medium, and that the hyperoxic exposure decreases the overall CoQ(1) reduction capacity via a depression in complex I activity.