SERCA2a controls the mode of agonist-induced intracellular Ca2+ signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells
SERCA2a controls the mode of agonist-induced intracellular Ca2+ signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells
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DOI：
10.1016/j.yjmcc.2010.12.016
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发表时间：
2011-04-01
影响因子：
5
通讯作者：
Lipskaia, Larissa
中科院分区：
文献类型：
--
作者：
Bobe, Regis;Hadri, Lahouaria;Lipskaia, Larissa
在血管中，张力是通过激动剂诱导的静止/收缩血管平滑肌细胞（VSMCs）的胞质Ca2+振荡来维持的。然而，在合成/增殖性vsmc中。Gq/磷酸肌苷受体偶联激动剂触发细胞质Ca2+的稳态增加，随后是储存操作钙入口（SOCE），转化为增殖相关转录因子NFAT的激活。在这里，我们报道了在人冠状动脉平滑肌细胞（hCASMCs）中，sarco/内质网钙atp酶2a型（SERCA2a）以hCASMCs的收缩形式表达，控制激动剂诱导的Ca2+瞬态和由此产生的下游信号通路的性质。事实上，通过基因转移在合成的hCASMCs中恢复SERCA2a的表达1)增加了Ca2+存储容量；2)修饰激动剂诱导的IP3R Ca2+释放从稳态到振荡模式(激动剂诱导的IP3R Ca2+信号频率在serca2a表达细胞（n = 39）中为11.66 +/- 1.40/100 s，而在对照细胞（n = 45）中为1.37 +/- 0.20/100 s, p
In blood vessels, tone is maintained by agonist-induced cytosolic Ca2+ oscillations of quiescent/contractile vascular smooth muscle cells (VSMCs). However, in synthetic/proliferative VSMCs. Gq/phosphoinositide receptor-coupled agonists trigger a steady-state increase in cytosolic Ca2+ followed by a Store Operated Calcium Entry (SOCE) which translates into activation of the proliferation-associated transcription factor NFAT. Here, we report that in human coronary artery smooth muscle cells (hCASMCs), the sarco/endoplasmic reticulum calcium ATPase type 2a (SERCA2a) expressed in the contractile form of the hCASMCs, controls the nature of the agonist-induced Ca2+ transient and the resulting down-stream signaling pathway. Indeed, restoring SERCA2a expression by gene transfer in synthetic hCASMCs 1) increased Ca2+ storage capacity; 2) modified agonist-induced IP3R Ca2+ release from steady-state to oscillatory mode (the frequency of agonist-induced IP3R Ca2+ signal was 11.66 +/- 1.40/100 s in SERCA2a-expressing cells (n = 39) vs 1.37 +/- 0.20/100 s in control cells (n = 45), p