Hypoxia selectively upregulates cation channels and increases cytosolic [Ca2+] in pulmonary, but not coronary, arterial smooth muscle cells
Hypoxia selectively upregulates cation channels and increases cytosolic [Ca2+] in pulmonary, but not coronary, arterial smooth muscle cells
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缺氧选择性上调阳离子通道并增加肺动脉平滑肌细胞（而非冠状动脉平滑肌细胞）中的胞质 [Ca(2 )]
DOI：
10.1152/ajpcell.00272.2017
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发表时间：
2018-04-01
影响因子：
5.5
通讯作者：
Yuan, Jason X-J
中科院分区：
文献类型：
--
作者：
He, Xi;Song, Shanshan;Yuan, Jason X-J
钙离子信号转导，特别是通过钙库操纵的钙离子内流（SOCE）和受体操纵的钙离子内流（ROCE）的机制。在急性低氧诱导的肺血管收缩和慢性低氧诱导的肺动脉高压的发展中起关键作用。本研究旨在验证慢性缺氧差异调节介导SOCK和ROCK [基质相互作用分子（STIM）]蛋白表达的假设。肺动脉（PASMC）和冠状动脉（CASMC）平滑肌细胞中的奥赖和经典瞬时受体电位通道TRPC 6]。CASMC和PASMC胞浆静息[Ca ~（2+）]（[Ca ~（2+）]（c）yt）和肌浆网贮存[Ca ~（2+）]无明显差异。海马的测量结果表明，CASMC和PASMC之间的线粒体生物能学（基础呼吸和ATP产生）的水平相似。PASMC的糖酵解明显高于CASMC。CASMC中环匹阿尼酸诱导的SOCE和OAG诱导的ROCE的幅度略大于PASMC，但显著大于PASMC。ATP和组胺引起的Ca 2+振荡频率和曲线下面积在CASMC也大于PASMC。Na+/Ca 2+交换介导的[Ca 2 +]（cyt）增加在CASMC和PASMC之间没有显著差异。STIM 1/2的基础蛋白表达水平。缺氧（3%O2）72 h后，STIM 1/STIM 2、Orai 1/Orai 2和TRPC 6蛋白表达显著上调，静息[Ca 2 +]（cyt）显著升高，而CASMC无明显变化。缺氧时钙库操纵和受体操纵钙通道的主要成分的不同反应是PASMC独特的内在特性，这可能是缺氧引起肺血管收缩和肺血管重构，而引起冠状动脉舒张的重要原因之一。
Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE). plays a critical role in the development of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension. This study aimed to test the hypothesis that chronic hypoxia differentially regulates the expression of proteins that mediate SOCK and ROCK [stromal interacting molecule (STIM). Orai, and canonical transient receptor potential channel TRPC6] in pulmonary (PASMC) and coronary (CASMC) artery smooth muscle cells. The resting cytosolic [Ca2+] ([Ca-2+](c)yt) and the stored [Ca2+] in the sarcoplasmic reticulum were not different in CASMC and PASMC. Seahorse measurement showed a similar level of mitochondrial bioenergetics (basal respiration and ATP production) between CASMC and PASMC. Glycolysis was significantly higher in PASMC than in CASMC. The amplitudes of cyclopiazonic acid-induced SOCE and OAG-induced ROCE in CASMC are slightly, but significantly, greater than in PASMC. The frequency and the area under the curve of Ca2+ oscillations induced by ATP and histamine were also larger in CASMC than in PASMC. Na+/Ca2+ exchanger-mediated increases in [Ca2+](cyt) did not differ significantly between CASMC and PASMC. The basal protein expression levels of STIM1/2. Orai1/2, and TRPC6 were higher in CASMC than in PASMC, but hypoxia (3% O-2 for 72 h) significantly upregulated protein expression levels of STIM1/STIM2, Orai1/Orai2, and TRPC6 and increased the resting [Ca2+](cyt) only in PASMC, but not in CASMC. The different response of essential components of store-operated and receptoroperated Ca2+ channels to hypoxia is a unique intrinsic property of PASMC, which is likely one of the important explanations why hypoxia causes pulmonary vasoconstriction and induces pulmonary vascular remodeling, but causes coronary vasodilation.