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Prerequisite role of persistent cell shrinkage in apoptosis of human epithelial cells

Shimizu T, Maeno E, Okada Y

Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585

Abstract

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 KC1 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.

Key words: Apoptosis;apoptotic volume decrease;persistent cell shrinkage;cell volume regulation;human epithelial cells

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Citing This Article：

Shimizu T, Maeno E, Okada Y. Prerequisite role of persistent cell shrinkage in apoptosis of human epithelial cells. Acta Physiol Sin 2007; 59 (4): 512-516 (in Chinese with English abstract).