Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis
Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis
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DOI：
10.1074/jbc.274.12.8261
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发表时间：
1999-03-19
影响因子：
4.8
通讯作者：
Murphy, E
中科院分区：
文献类型：
--
作者：
Jayadev, S;Petranka, JG;Murphy, E
叙利亚仓鼠胚胎细胞的一种肿瘤前变体sup（+）表现出内质网钙水平降低，随后在低血清条件下发生细胞凋亡（普雷斯顿，G，A，Barrett，J，C，Biermann，J，A，和Murphy，E，（1997）Cancer Res.57，537-542）。内质网钙的这种减少似乎是由于，至少部分是由于减少了质膜上的容性钙进入。因此，我们研究了抑制容量性钙离子内流本身是否会减少内质网钙离子并诱导细胞凋亡。我们发现用SKF 96365（30-100 μ M）或细胞不渗透的1，2-双（邻氨基-5-溴苯氧基）乙烷-N，N，N ′，N ′-四乙酸（5-10 mM）处理能够在凋亡通常不发生的条件下诱导细胞凋亡。由于以前的工作涉及囊泡贩运作为调节能力钙进入的机制，我们研究了囊泡贩运的破坏是否会导致能力钙进入减少和随后的细胞凋亡。与低血清诱导的细胞凋亡一致，我们观察到细胞内囊泡的积累，表明囊泡运输失调。（30-100 nM），一种内体质子ATP酶抑制剂，产生囊泡的积累，减少容量进入，并诱导细胞凋亡，这些数据表明，囊泡转运的失调会导致容量性钙离子进入减少，从而导致细胞凋亡。
A preneoplastic variant of Syrian hamster embryo cells, sup(+), exhibits decreased endoplasmic reticulum calcium levels and subsequently undergoes apoptosis in low serum conditions (Preston, G, A, Barrett, J, C,, Biermann, J, A, and Murphy, E, (1997) Cancer Res. 57, 537-542). This decrease in endoplasmic reticulum calcium appears to be due, at least in part, to reduced capacitative calcium entry at the plasma membrane. Thus we investigated whether inhibition of capacitative calcium entry per se could reduce endoplasmic reticulum calcium and induce apoptosis of cells. We find that treatment with either SKF96365 (30-100 mu M) Or cell-impermeant 1,2-bis(o-amino-5-bromophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5-10 mM) is able to induce apoptosis of cells in conditions where apoptosis does not normally occur. Because previous work has implicated vesicular trafficking as a mechanism of regulating capacitative calcium entry, we investigated whether disruption of vesicular trafficking could lead to decreased capacitative calcium entry and subsequent apoptosis of cells. Coincident with low serum-induced apoptosis, we observed an accumulation of vesicles within the cell, suggesting deregulated vesicle trafficking, Treatment of cells with bafilomycin (30-100 nM), an inhibitor of the endosomal proton ATPase, produced an accumulation of vesicles, decreased capacitative entry, and induced apoptosis, These data suggest that deregulation of vesicular transport results in reduced capacitative calcium entry which in turn results in apoptosis.