Kuo T H, Liu B F, Yu Y, Wuytack F, Raeymaekers L, Tsang W
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cell Calcium. 1997 Jun;21(6):399-408. doi: 10.1016/s0143-4160(97)90051-8.
The plasma membrane calcium pump (PMCA) and sarco(endo)plasmic reticular calcium pump (SERCA) are important components of the Ca2+ homeostasis system responsible for intracellular Ca2+ signaling, yet the factors which govern their expression remain unclear. Recently, we have found that overexpression of PMCA by a gene transfection approach caused a down-regulation of the SERCA pump [Liu B.F., Xu X., Fridman R., Muallem S., Kuo T.H. Consequences of functional expression of the plasma membrane calcium pump isoform 1a. J Biol Chem 1996; 271: 5536-5544]. The results suggest an interdependence between PMCA and SERCA gene expression which has prompted us to investigate further on the mechanisms that regulate the expression of these Ca2+ pump genes in various cultured cell lines. In the present study, we have analyzed the isoforms of the PMCA and SERCA in different cells and presented evidence in favor of a co-induction of the PMCA and SERCA gene expression by second messengers, such as protein kinase C, cAMP, and Ca2+. Ectopic expression of PMCA or SERCA led to downregulation of the endogenous forms of both pumps. Changes in the level of mRNAs were paralleled by corresponding altered pump protein contents. The Ca(2+)-mediated increase of gene expression is accompanied by increased transcription rates as indicated by nuclear run-on assay. The co-ordinated induction of the PMCA and SERCA gene expression by thapsigargin was not blocked by the cytosolic application of the Ca2+ chelator BAPTA. We conclude that genes encoding components of the major Ca2+ transport pathways, including pumps and IP3 receptor channels, are regulatorally linked and this link is provided by the Ca2+ load of the ER store. This study points to the importance of gene expression as an integral component in the regulation of cellular Ca2+ homeostasis.
质膜钙泵（PMCA）和肌浆（内质）网钙泵（SERCA）是负责细胞内钙信号传导的钙稳态系统的重要组成部分，但其表达调控因素仍不清楚。最近，我们发现通过基因转染方法过表达PMCA会导致SERCA泵下调[Liu B.F., Xu X., Fridman R., Muallem S., Kuo T.H. 质膜钙泵同工型1a功能表达的后果。《生物化学杂志》1996年；271: 5536 - 5544]。结果表明PMCA和SERCA基因表达之间存在相互依赖性，这促使我们进一步研究在各种培养细胞系中调节这些钙泵基因表达的机制。在本研究中，我们分析了不同细胞中PMCA和SERCA的同工型，并提供证据支持第二信使如蛋白激酶C、cAMP和Ca2 +对PMCA和SERCA基因表达的共同诱导作用。PMCA或SERCA的异位表达导致两种泵内源性形式的下调。mRNA水平的变化与相应改变的泵蛋白含量平行。如核转录分析所示，Ca(2 +)介导的基因表达增加伴随着转录速率的提高。毒胡萝卜素对PMCA和SERCA基因表达的协同诱导作用不会被胞质中应用Ca2 +螯合剂BAPTA所阻断。我们得出结论，编码主要钙转运途径成分（包括泵和IP3受体通道）的基因在调节上是相互关联的，这种关联是由内质网钙库的钙负荷提供的。这项研究指出基因表达作为细胞钙稳态调节中一个不可或缺的组成部分的重要性。
