Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids.
Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids.
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DOI：
10.1161/atvbaha.110.205666
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Beech DJ
中科院分区：
文献类型：
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作者：
Al-Shawaf E;Naylor J;Taylor H;Riches K;Milligan CJ;O'Regan D;Porter KE;Li J;Beech DJ
氧化磷脂是炎症和包括动脉粥样硬化在内的相关疾病的关键因子，但细胞对这些因子的最初接受机制尚不清楚。本研究的目的是确定氧化磷脂1-棕榈酰基-2-戊二酰磷脂酰胆碱(PGPC)和1-棕榈酰基-2-氧戊酰磷脂酰胆碱(POVPC)是否是钙通透通道的靶标。低微摩尔浓度的PGPC和POVPC可引起高表达人瞬时受体电位Canonical 5(TRPC5)的HEK 293细胞内钙的升高，但不能诱导人瞬时受体电位Melastatin 2或3的表达。电生理实验证实了TRPC5的刺激。为了研究与内源性通道的相关性，我们研究了冠状动脉搭桥术患者血管平滑肌细胞的增殖。PGPC和POVPC诱导的钙内流可被抗TRPC5或抗TRPC1抗体或显性阴性突变体TRPC5抑制。未见钙释放。这种效应在功能上是相关的，因为它促进了细胞迁移。PGPC和POVPC的作用依赖于Gi/o蛋白，但尚未发现氧化磷脂的G蛋白偶联受体。这些数据表明，对含有TRPC5的钙离子通道的刺激是细胞对氧化磷脂反应的早期事件，这种反应与细胞迁移有关，需要一种未知的G蛋白偶联受体。
Oxidized phospholipids are key factors in inflammation and associated diseases including atherosclerosis yet the initial reception mechanisms for cellular responses to the factors are poorly understood. The objective of this study was to determine if calcium-permeable channels are targets for the oxidized phospholipids, 1-palmitoyl-2-glutaroyl-phosphatidylcholine (PGPC) and 1-palmitoyl-2-oxovaleroyl-phosphatidylcholine (POVPC). Low micromolar concentrations of PGPC and POVPC evoked rises in intracellular calcium in HEK 293 cells over-expressing human Transient Receptor Potential Canonical 5 (TRPC5) but not human Transient Receptor Potential Melastatin 2 or 3. Electrophysiological experiments confirmed stimulation of TRPC5. To investigate relevance to endogenous channels we studied proliferating vascular smooth muscle cells from patients undergoing coronary artery bypass surgery. PGPC and POVPC elicited calcium entry that was inhibited by anti-TRPC5 or anti-TRPC1 antibodies or dominant-negative mutant TRPC5. Calcium-release did not occur. The effect was functionally relevant because it enhanced cell migration. Actions of PGPC and POVPC depended on Gi/o proteins but not previously identified G protein coupled receptors for oxidized phospholipids. The data suggest that stimulation of calcium-permeable TRPC5-containing channels is an early event in cellular responses to oxidized phospholipids that couples to cell migration and requires an unidentified G protein coupled receptor.