Shimizu Takahiro, Maeno Emi, Okada Yasunobu
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
Sheng Li Xue Bao. 2007 Aug 25;59(4):512-6.
Persistent cell volume reduction is a major hallmark of apoptosis. Recent studies have demonstrated that cell volume reduction is not a passive, secondary event of the apoptotic cell death process. Whole-cell shrinkage, termed apoptotic volume decrease (AVD), takes place soon after stimulation with apoptogen and precedes caspase activation, DNA and cell fragmentation in a variety of cell types including human epithelial cells. The AVD induction is the result of KCl efflux attained by activation of K(+) and Cl(-) channels. Inhibition of AVD induction leads to rescue of the cells from apoptosis. Since the AVD process is coupled to dysfunction of the regulatory volume increase (RVI), apoptotic cells undergo persistent cell shrinkage in human epithelial HeLa cells. When the RVI mechanism was impaired, hypertonic stress itself induced not only persistent cell shrinkage but also apoptotic cell death in HeLa cells. Even under normotonic apoptogen-free conditions, exposure of HeLa cells to Na(+)- or Cl(-)-deficient solution alone can bring about persistent cell shrinkage and thereafter apoptotic cell death. Thus, it is concluded that persistent cell shrinkage, which comprises AVD induction and RVI dysfunction, is a prerequisite to apoptosis induction in human epithelial cells.
持续性细胞体积减小是细胞凋亡的一个主要标志。最近的研究表明，细胞体积减小并非细胞凋亡死亡过程中的一个被动的继发性事件。全细胞收缩，即凋亡性体积减小（AVD），在用凋亡原刺激后很快就会发生，且在包括人上皮细胞在内的多种细胞类型中，先于半胱天冬酶激活、DNA和细胞碎片化。AVD的诱导是通过激活钾离子（K(+)）和氯离子（Cl(-)）通道实现钾离子外流的结果。抑制AVD诱导可使细胞免于凋亡。由于AVD过程与调节性体积增加（RVI）功能障碍相关联，人上皮性HeLa细胞中的凋亡细胞会经历持续性细胞收缩。当RVI机制受损时，高渗应激本身不仅会诱导HeLa细胞持续性细胞收缩，还会导致凋亡性细胞死亡。即使在无凋亡原的等渗条件下，仅将HeLa细胞暴露于缺乏钠离子（Na(+)）或氯离子（Cl(-)）的溶液中，也会导致持续性细胞收缩，随后发生凋亡性细胞死亡。因此，可以得出结论，由AVD诱导和RVI功能障碍组成的持续性细胞收缩是诱导人上皮细胞凋亡的一个先决条件。
