Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells.
Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells.
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DOI：
10.1016/j.resp.2010.08.008
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发表时间：
2010-12-31
影响因子：
2.3
通讯作者：
Zheng, Yun-Min
中科院分区：
文献类型：
--
作者：
Wang, Yong-Xiao;Zheng, Yun-Min
关键词：
缺氧引起肺动脉平滑肌细胞（PASMCs）[Ca ~（2+）]i的大量增加和伴随的收缩，但不引起体动脉SMC的收缩。不同的反应满足了这两种不同的血管肌细胞各自的功能需求;然而，其潜在的分子机制尚不清楚。我们和其他研究人员提供了大量证据表明，电压依赖性K+（KV）通道、经典瞬时受体电位（TRPC）通道、兰尼碱受体Ca 2+释放通道（RyRs）、环腺苷二磷酸核糖、FK 506结合蛋白12.6、蛋白激酶C、NADPH氧化酶和活性氧（ROS）是PASMCs和HPV中[Ca 2 +]i缺氧增加的重要效应物和信号中间体，但它们可能不是肺和全身血管肌细胞中不同细胞反应的主要基础。缺氧可显著增加PASMCs线粒体ROS的产生，通过开放RyRs诱导细胞内Ca 2+释放，并通过抑制KV通道和激活TRPC通道引起细胞外Ca 2+内流，导致PASMCs和HPV细胞内[Ca 2 +]i大量增加。相反，缺氧对系统性SMC中线粒体ROS的产生没有影响或影响很小，从而导致[Ca 2 +]i和收缩没有变化或增加可忽略不计。进一步的初步研究表明，线粒体复合物III中的Rieske铁硫蛋白可能是PASMCs和HPV中[Ca 2 +]i缺氧增加的关键初始分子决定因素，表明其在肺动脉和体动脉肌细胞响应缺氧刺激的不同细胞变化中可能起重要作用。所有这些研究结果大大提高了我们对不同的肺和体循环系统的血管平滑肌细胞的差异缺氧Ca 2+和收缩反应的分子过程的理解。
Hypoxia causes a large increase in [Ca2+]i and attendant contraction in pulmonary artery smooth muscle cells (PASMCs), but not in systemic artery SMCs. The different responses meet the respective functional needs in these two distinct vascular myocytes; however, the underlying molecular mechanisms are not well known. We and other investigators have provided extensive evidence to reveal that voltage-dependent K+ (KV) channels, canonical transient receptor potential (TRPC) channels, ryanodine receptor Ca2+ release channels (RyRs), cyclic adenosine diphosphate-ribose, FK506 binding protein 12.6, protein kinase C, NADPH oxidase and reactive oxygen species (ROS) are the essential effectors and signaling intermediates in the hypoxic increase in [Ca2+]i in PASMCs and HPV, but they may not primarily underlie the diverse cellular responses in pulmonary and systemic vascular myocytes. Hypoxia significantly increases mitochondrial ROS generation in PASMCs, which can induce intracellular Ca2+ release by opening RyRs, and may also cause extracellular Ca2+ influx by inhibiting KV channels and activating TRPC channels, leading to a large increase in [Ca2+]i in PASMCs and HPV. In contrast, hypoxia has no or a minor effect on mitochondrial ROS generation in systemic SMCs, thereby causing no change or a negligible increase in [Ca2+]i and contraction. Further preliminary work indicates that Rieske iron–sulfur protein in the mitochondrial complex III may perhaps serve as a key initial molecular determinant for the hypoxic increase in [Ca2+]i in PASMCs and HPV, suggesting its potential important role in different cellular changes to respond to hypoxic stimulation in pulmonary and systemic artery myocytes. All these findings have greatly improved our understanding of the molecular processes for the differential hypoxic Ca2+ and contractile responses in vascular SMCs from distinct pulmonary and systemic circulation systems.
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影响因子：
--
作者：
JIN, NJ;PACKER, CS;RHOADES, RA
通讯作者：
RHOADES, RA
影响因子：
20.1
作者：
ARCHER, SL;HUANG, J;WEIR, EK
通讯作者：
WEIR, EK
影响因子：
6.1
作者：
Kang, TM;Park, MK;Uhm, DY
通讯作者：
Uhm, DY
DOI：
10.1164/ajrccm/144.4.884
发表时间：
1991-10-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
HASUNUMA, K;RODMAN, DM;MCMURTRY, IF
通讯作者：
MCMURTRY, IF
影响因子：
6.1
作者：
Kang, TM;Park, MK;Uhm, DY
通讯作者：
Uhm, DY