Primary role of mitochondrial Rieske iron-sulfur protein in hypoxic ROS production in pulmonary artery myocytes.
Primary role of mitochondrial Rieske iron-sulfur protein in hypoxic ROS production in pulmonary artery myocytes.
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DOI：
10.1016/j.freeradbiomed.2011.01.010
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发表时间：
2011-04-15
影响因子：
7.4
通讯作者：
Wang, Yong-Xiao
中科院分区：
文献类型：
--
作者：
Korde, Amit S.;Yadav, Vishal R.;Zheng, Yun-Min;Wang, Yong-Xiao
关键词：
本研究旨在探讨：（1）缺氧是否直接影响肺动脉平滑肌细胞（PASMCs）线粒体和线粒体复合物III的活性氧产生;（2）复合物III中的Rieske铁硫蛋白是否介导缺氧性活性氧产生，导致缺氧性肺血管收缩（HPV）。我们的数据，第一次，表明缺氧显着提高ROS的生产，测量标准的ROS指示剂二氯二氢荧光素/二乙酸酯，在分离的线粒体PASMCs。使用新开发的特异性ROS生物传感器pHyPer的研究发现，缺氧也会增加分离的PASMCs中线粒体ROS的产生。在分离的复合物III中也观察到低氧ROS的产生。Rieske铁-硫蛋白沉默使用siRNA废除了缺氧ROS形成在分离的PASM复合物III，线粒体和细胞，而Rieske铁-硫蛋白过表达产生相反的效果。Rieske铁硫蛋白沉默抑制PASMCs缺氧性[Ca 2 +]i升高和分离的PA缺氧性血管收缩。这些发现共同提供了新的证据，线粒体是PASMCs中的直接缺氧靶点，其中复合物III中的Rieske铁硫蛋白可能作为介导缺氧ROS产生的重要的主要分子，导致PASMCs和HPV中[Ca 2 +]i增加。
This study was designed to determine whether: (1) hypoxia could directly affect ROS production in isolated mitochondria and mitochondrial complex III from pulmonary artery smooth muscle cells (PASMCs), and (2) Rieske iron-sulfur protein in the complex III might mediate hypoxic ROS production, leading to hypoxic pulmonary vasoconstriction (HPV). Our data, for the first time, demonstrate that hypoxia significantly enhances ROS production, measured by the standard ROS indicator dichlorodihydrofluorescein/diacetate, in isolated mitochondria from PASMCs. Studies using the newly-developed, specific ROS biosensor pHyPer have found that hypoxia increases mitochondrial ROS generation as well in isolated PASMCs. The hypoxic ROS production has also been observed in isolated complex III. Rieske iron-sulfur protein silencing using siRNAs abolishes the hypoxic ROS formation in isolated PASM complex III, mitochondria and cells, while Rieske iron-sulfur protein overexpression produces the opposite effect. Rieske iron-sulfur protein silencing inhibits the hypoxic increase in [Ca2+]i in PASMCs and hypoxic vasoconstriction in isolated PAs. These findings together provide novel evidence that mitochondria are the direct hypoxic targets in PASMCs, in which Rieske iron-sulfur protein in the complex III may serve as an essential, primary molecule that mediates the hypoxic ROS generation, leading to an increase in [Ca2+]i in PASMCs and HPV.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
4.8
作者：
Jung, Hye Jin;Shim, Joong Sup;Kwon, Ho Jeong
通讯作者：
Kwon, Ho Jeong
影响因子：
20.1
作者：
ARCHER, SL;HUANG, J;WEIR, EK
通讯作者：
WEIR, EK
影响因子：
4.5
作者：
Li, Xiao-Qiang;Zheng, Yun-Min;Rathore, Rakesh;Ma, Jianjie;Takeshima, Hiroshi;Wang, Yong-Xiao
通讯作者：
Wang, Yong-Xiao
影响因子：
6.6
作者：
Guzy, Robert D.;Mack, Matthew M.;Schumacker, Paul T.
通讯作者：
Schumacker, Paul T.