S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells
S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells
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DOI：
10.1152/ajpcell.00350.2010
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发表时间：
2011-04-01
影响因子：
5.5
通讯作者：
Waeber, Christian
中科院分区：
文献类型：
--
作者：
Hopson, Kristen Park;Truelove, Jessica;Waeber, Christian
Hopson KP，Truelove J，Chun J，Wang Y，Waeber C.S1P通过受体和非受体介导的途径激活血管平滑肌细胞内钙内流。Am J Physiol Cell Physiol 300：C919-C926,2011。首次发表于2011年1月26日；doi:10.1152/ajpcell.00350.2010.-Sphingosine-1-phosphate(S1P)已被证明通过G蛋白偶联受体和细胞内第二信使途径调节细胞内钙离子。S1P激活血管平滑肌细胞(VSMCs)储存操作钙内流(SOCE)的确切机制尚不完全清楚。由于鞘磷脂和钙离子调节血管平滑肌细胞的增殖和收缩，因此研究S1P和SOCE之间的联系可能为血管疾病的治疗提供新的靶点。我们发现S1P在VSMC中触发了STIM1斑点的形成和SOCE。2-氨基乙氧基二苯硼酸酯(2-APB)、己烯雌酚(DES)和Gd~(3+)可抑制S1P激活的SOCE。在缺乏S1P(2)或S1P(3)受体的VSMC中观察到SOCE，提示S1P通过多条信号通路发挥作用。事实上，细胞外和细胞内应用S1P都以2-APB敏感的方式增加了转染STIM1-黄色荧光蛋白的VSMCs细胞的总内反射荧光信号。这些数据，以及2-APB、DES和Gd3+都抑制S1P诱导的脑动脉收缩的事实，表明SOCE在体内调节S1P诱导的血管收缩。最后，S1P诱导的增殖期SOCE大于收缩VSMCs，这与STIM1、Orai1、S1P(1)和S1P(3)受体mRNA的增加有关。这些数据表明，S1P可以通过两种受体和一种新的细胞内途径来激活SOCE。由于S1P诱导的SOCE导致血管收缩，并在增殖期VSMCs中增加，S1P/SOCE信号可能在动脉粥样硬化和糖尿病等血管功能障碍中发挥作用。
Hopson KP, Truelove J, Chun J, Wang Y, Waeber C. S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells. Am J Physiol Cell Physiol 300: C919-C926, 2011. First published January 26, 2011; doi:10.1152/ajpcell.00350.2010.-Sphingosine-1-phosphate (S1P) has been shown to modulate intracellular Ca2+ through both G protein-coupled receptors and intracellular second messenger pathways. The precise mechanism by which S1P activates store-operated calcium entry (SOCE) in vascular smooth muscle cells (VSMCs) has not been fully characterized. Because sphingolipids and Ca2+ modulate proliferation and constriction in VSMCs, characterizing the connection between S1P and SOCE may provide novel therapeutic targets for vascular diseases. We found that S1P triggered STIM1 puncta formation and SOCE in VSMCs. S1P-activated SOCE was inhibited by 2-aminoethoxydiphenyl borate (2-APB), diethylstilbestrol (DES), and gadolinium (Gd3+). SOCE was observed in VSMCs lacking either S1P(2) or S1P(3) receptors, suggesting that S1P acts via multiple signaling pathways. Indeed, both extracellular and intracellular S1P application increased the total internal reflection fluorescence signal in VSMCs cells transfected with STIM1-yellow fluorescent protein in a 2-APB-sensitive manner. These data, and the fact that 2-APB, DES, and Gd3+ all inhibited S1P-induced cerebral artery constriction, suggest that SOCE modulates S1P-induced vasoconstriction in vivo. Finally, S1P-induced SOCE was larger in proliferative than in contractile VSMCs, correlating with increases in STIM1, Orai1, S1P(1), and S1P(3) receptor mRNA. These data demonstrate that S1P can act through both receptors and a novel intracellular pathway to activate SOCE. Because S1P-induced SOCE contributes to vessel constriction and is increased in proliferative VSMCs, it is likely that S1P/SOCE signaling in proliferative VSMCs may play a role in vascular dysfunction such as atherosclerosis and diabetes.