Regulation of SERCA Ca2+ pump expression by cytoplasmic Ca2+ in vascular smooth muscle cells.
Regulation of SERCA Ca2+ pump expression by cytoplasmic Ca2+ in vascular smooth muscle cells.
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血管平滑肌细胞中细胞质 Ca2+ 对 SERCA Ca2+ 泵表达的调节。
DOI：
10.1152/ajpcell.2001.280.4.c843
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Lytton,J
中科院分区：
文献类型：
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作者：
Wu,KD;Bungard,D;Lytton,J
血管平滑肌细胞（VSMC）表达肌浆或内质网Ca2+- atp酶（SERCA）泵的三种异构体；SERCA2b占主导地位（91%），而SERCA2a（6%）和SERCA3（3%）的数量要少得多。Tg或A-23187使编码SERCA2b的mRNA水平升高4 - 5倍；SERCA3增加了约10倍，而SERCA2a不变。Ca2+螯合阻止tg诱导的SERCA2b的增加，而Ca2+升高本身增加了SERCA2b的表达。这些反应与78 kda葡萄糖调节蛋白/免疫球蛋白结合蛋白（grp78/BiP）的反应不一致，grp78/BiP是一种内质网应激反应蛋白。SERCA2b mRNA的升高比观察到的信息稳定性的增加要大得多。Tg诱导SERCA2b不需要蛋白质合成，也不受钙调磷酸酶、蛋白激酶C、Ca2+/钙调蛋白依赖性蛋白激酶或酪氨酸蛋白激酶抑制剂的影响。用非选择性蛋白激酶抑制剂H-7治疗可以阻止tg诱导的SERCA2b表达的发生，而另一种非选择性抑制剂staurosporine则没有效果。我们得出的结论是，胞质Ca2+的变化通过一种目前尚未确定的、对h -7敏感但对staurosporine不敏感的蛋白激酶的机制来控制VSMC中SERCA2b的表达。
Vascular smooth muscle cells (VSMC) express three isoforms of the sarcoplasmic or endoplasmic reticulum Ca2+-ATPase (SERCA) pump; SERCA2b predominates (91%), whereas SERCA2a (6%) and SERCA3 (3%) are present in much smaller amounts. Treatment with thapsigargin (Tg) or A-23187 increased the level of mRNA encoding SERCA2b four- to fivefold; SERCA3 increased about 10-fold, whereas SERCA2a was unchanged. Ca2+chelation prevented the Tg-induced SERCA2b increase, whereas Ca2+elevation itself increased SERCA2b expression. These responses were discordant with those of 78-kDa glucose-regulated protein/immunoglobulin-binding protein (grp78/BiP), an endoplasmic reticulum stress-response protein. SERCA2b mRNA elevation was much larger than could be accounted for by the observed increase in message stability. The induction of SERCA2b by Tg did not require protein synthesis, nor was it affected by inhibitors of calcineurin, protein kinase C, Ca2+/calmodulin-dependent protein kinase, or tyrosine protein kinases. Treatment with the nonselective protein kinase inhibitor H-7 prevented Tg-induced SERCA2b expression from occurring, whereas another nonselective inhibitor, staurosporine, was without effect. We conclude that changes in cytosolic Ca2+control the expression of SERCA2b in VSMC via a mechanism involving a currently uncharacterized, H-7-sensitive but staurosporine-insensitive, protein kinase.