Endoplasmic reticulum calcium release engages Bax translocation in cortical astrocytes.
Endoplasmic reticulum calcium release engages Bax translocation in cortical astrocytes.
复制标题
内质网钙释放参与皮质星形胶质细胞中的 Bax 易位。
DOI：
10.1007/s11064-011-0411-8
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发表时间：
2011
影响因子：
4.4
通讯作者：
Smaili,SS
中科院分区：
文献类型：
--
作者：
Morales,AP;Carvalho,ACP;Monteforte,PT;Hirata,H;Han,SW;Hsu,Y-T;Smaili,SS
细胞凋亡是一种高度复杂的细胞死亡形式，可由钙离子稳态的变化触发。Bcl2家族的成员可以调节细胞内的细胞凋亡和钙离子的分布。Bax是该家族中的一个促凋亡成员，它在细胞质中结构性表达和溶解，并在凋亡诱导下移位到线粒体膜。然而，目前尚不清楚细胞内的钙储存和选择性的钙释放是否能够调控Bax的转运。本研究的目的是探讨大脑皮层星形胶质细胞内钙贮量与Bax转位的关系。结果表明，经典的细胞凋亡诱导剂星形孢子素在Bax转位之前引起胞浆内钙离子的升高。另一方面，去甲肾上腺素或thapsigargin等内质网钙离子激动剂可引起Bax易位，而乙酰氰化物-对-三氟甲氧基苯肼引起的线粒体钙释放不能引起Bax穿孔。此外，微量注射1，4，5-三磷酸肌醇可诱导Bax易位。综上所述，我们的结果表明，在Bax高表达的皮质星形胶质细胞中，内质网钙离子释放可能诱导Bax反式激活并特异性地控制细胞凋亡。
Apoptosis is a highly complex form of cell death that can be triggered by alterations in Ca2+homeostasis. Members of the Bcl-2 family may regulate apoptosis and modulate Ca2+distribution within intracellular compartments. Bax, a proapoptotic member of the family, is constitutively expressed and soluble in the cytosol and, under apoptotic induction, translocates to mitochondrial membranes. However, it is not clear if the intracellular Ca2+stores and selective Ca2+releases can modulate or control Bax translocation. The aim of this study was to investigate the relation of intracellular Ca2+stores with Bax translocation in rat cortical astrocytes. Results show that the classical apoptotic inducer, staurosporine, caused high elevations of cytosolic Ca2+that precede Bax translocation. On the other hand, agents that mobilize Ca2+from endoplasmic reticulum such as noradrenaline or thapsigargin, induced Bax translocation, while mitochondrial Ca2+release evoked by carbonyl cyanide-p-(trifluoromethoxyphenyl) hydrazone was not able to cause Bax punctation. In addition, microinjection of inositol 1,4,5- trisphosphate induced Bax translocation. Taken together, our results show that in Bax overexpressing cortical astrocytes, endoplasmic reticulum-Ca2+release may induce Bax transactivation and specifically control apoptosis.