Dysfunction of regulatory volume increase is a key component of apoptosis
Dysfunction of regulatory volume increase is a key component of apoptosis
复制标题
DOI：
10.1016/j.febslet.2006.10.074
复制
发表时间：
2006-11-27
期刊：
影响因子：
3.5
通讯作者：
Okada, Yasunobu
中科院分区：
文献类型：
--
作者：
Maeno, Emi;Takahashi, Nobuyuki;Okada, Yasunobu
持续的细胞萎缩是凋亡细胞死亡的主要标志。在凋亡细胞中，整个细胞体积减少，称为凋亡体积减少（AVD），直到细胞分裂。在非凋亡条件下，人上皮HeLa细胞暴露于高渗溶液诱导渗透收缩后表现出缓慢的调节体积增加（RVI）。然而，当用Fas配体、tnf - α或staurosporine诱导AVD时，发现HeLa细胞无法进行RVI。当联合应用Na+/H+交换剂（NHE）和阴离子交换阻滞剂抑制RVI时，高渗应激诱导HeLa细胞长时间收缩，随后caspase-3激活。高渗性也诱导缺乏RVI反应的nhe1缺陷PS120成纤维细胞凋亡。当NHE1转染这些细胞恢复RVI时，高渗性诱导的细胞凋亡完全被阻止。因此，RVI功能障碍是AVD持续存在和诱导细胞凋亡的必要条件。(c) 2006年欧洲生化学会联合会。Elsevier B.V.版权所有。
Sustained cell shrinkage is a major hallmark of apoptotic cell death. In apoptotic cells, whole cell volume reduction, called apoptotic volume decrease (AVD), proceeds until fragmentation of cells. Under non-apoptotic conditions, human epithelial HeLa cells exhibited a slow regulatory volume increase (RVI) after osmotic shrinkage induced by exposure to hypertonic solution. When AVD was induced by treatment with a Fas ligand, TNF-alpha or staurosporine, however, it was found that HeLa cells failed to undergo RVI. When RVI was inhibited by combined application of Na+/H+ exchanger (NHE) and anion exchanger blockers, hypertonic stress induced prolonged shrinkage followed by caspase-3 activation in HeLa cells. Hypertonicity also induced apoptosis in NHE1-deficient PS120 fibroblasts, which lack the RVI response. When RVI was restored by transfection of these cells with NHE1, hypertonicity-induced apoptosis was completely prevented. Thus, it is concluded that RVI dysfunction is indispensable for the persistence of AVD and induction of apoptosis. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.