Mitochondrial reserve capacity in endothelial cells: The impact of nitric oxide and reactive oxygen species.
Mitochondrial reserve capacity in endothelial cells: The impact of nitric oxide and reactive oxygen species.
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DOI：
10.1016/j.freeradbiomed.2010.01.015
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发表时间：
2010-04-01
影响因子：
7.4
通讯作者：
Darley-Usmar, Victor M.
中科院分区：
文献类型：
--
作者：
Dranka, Brian P.;Hill, Bradford G.;Darley-Usmar, Victor M.
关键词：
内皮细胞不被认为是一个主要的需要能量的器官，但内皮细胞有一个广泛的线粒体网络。这表明线粒体功能在这些细胞对压力和信号的反应中可能是重要的。在这项研究中，我们使用细胞外流量分析来测量贴壁的牛主动脉内皮细胞(BAEC)的线粒体功能。在基础条件下，BAEC仅利用其最大呼吸量的~35%。我们计算出，这代表状态3和状态4之间的中间呼吸状态，我们将其定义为表观状态等于3.64。有趣的是，这些细胞的表观呼吸控制比(最大线粒体耗氧量/非ADP连接的呼吸)约为23，大大高于经常获得的分离线粒体的呼吸控制率。这些结果表明，内皮细胞中的线粒体是高度偶联的，具有相当大的生物能量储备。由于内皮细胞在血管疾病过程中同时暴露于活性氧和氮物种(ROS/RNS)，我们假设这种储备能力在应对氧化应激中是重要的。为了测试这一点，我们将BAEC单独或联合暴露于NO或ROS。我们发现，暴露于无毒浓度的NO或2，3-二甲氧基-1，4-萘醌(DMNQ)产生的低水平过氧化氢对线粒体的基本功能几乎没有影响，但这两种处理都可逆地降低了线粒体的储备能力。然而，NO和DMNQ联合处理会导致储备能力不可逆转的丧失，并与细胞死亡有关。这些数据与内皮细胞线粒体储备能力在应对氧化应激中的关键作用是一致的。
The endothelium is not considered to be a major energy requiring organ, but nevertheless endothelial cells have an extensive mitochondrial network. This suggests that mitochondrial function may be important in response to stress and signaling in these cells. In this study, we used extracellular flux analysis to measure mitochondrial function in adherent bovine aortic endothelial cells (BAEC). Under basal conditions, BAEC use only ~35% of their maximal respiratory capacity. We calculate that this represents an intermediate respiratory State between States 3 and 4 which we define as Stateapparent equal to 3.64. Interestingly, the apparent respiratory control ratio (maximal mitochondrial oxygen consumption/non-ADP linked respiration) in these cells is on the order of 23 which is substantially higher than that which is frequently obtained with isolated mitochondria. These results suggest that mitochondria in endothelial cells are highly coupled and possess a considerable bioenergetic reserve. Since endothelial cells are exposed to both reactive oxygen and nitrogen species (ROS/RNS) in the course of vascular disease, we hypothesized that this reserve capacity is important in responding to oxidative stress. To test this, we exposed BAEC to NO or ROS alone or in combination. We found that exposure to non-toxic concentrations of NO or low levels of hydrogen peroxide generated from 2,3-dimethoxy-1,4-napthoquinone (DMNQ) had little impact on basal mitochondrial function but both treatments reversibly decreased mitochondrial reserve capacity. However, combined NO and DMNQ treatment resulted in an irreversible loss of reserve capacity and was associated with cell death. These data are consistent with a critical role of mitochondrial reserve capacity in endothelial cells in responding to oxidative stress.
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影响因子：
7.4
作者：
Gerencser, Akos A.;Neilson, Andy;Choi, Sung W.;Edman, Ursula;Yadava, Nagendra;Oh, Richard J.;Ferrick, David A.;Nicholls, David G.;Brand, Martin D.
通讯作者：
Brand, Martin D.
影响因子：
5.5
作者：
Cooper, Chris E.;Giulivi, Cecilia
通讯作者：
Giulivi, Cecilia
影响因子：
13.8
作者：
Cooper, CE;Patel, RP;Darley-Usmar, VM
通讯作者：
Darley-Usmar, VM
DOI：
10.1073/pnas.152149699
发表时间：
2002-08-06
影响因子：
11.1
作者：
Joshi, MS;Ferguson, TB;Lancaster, JR
通讯作者：
Lancaster, JR
影响因子：
4.8
作者：
Hwang, J;Saha, A;Jo, H
通讯作者：
Jo, H