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Dysfunction of regulatory volume increase is a key component of apoptosis
Author(s) -
Maeno Emi,
Takahashi Nobuyuki,
Okada Yasunobu
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.10.074
Subject(s) - apoptosis , hela , staurosporine , microbiology and biotechnology , chemistry , transfection , tonicity , programmed cell death , cell , biology , biochemistry , signal transduction , gene , protein kinase c
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‐α 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.