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Marginal blebbing during the early stages of TNF‐induced apoptosis indicates alteration in actomyosin contractility
Author(s) -
Domnina L.V.,
Ivanova O.Y.,
Pletjushkina O.Y.,
Fetisova E.K.,
Chernyak B.V.,
Skulachev V.P.,
Vasiliev J.M.
Publication year - 2004
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2004.03.017
Subject(s) - microbiology and biotechnology , microfilament , actin , biology , apoptosis , staurosporine , bleb (medicine) , contractility , cell , cytoskeleton , kinase , protein kinase a , biochemistry , endocrinology , neuroscience , trabeculectomy , glaucoma
Dynamics of alterations of cell surface topography during TNF‐induced apoptosis of HeLa cells was examined by phase‐contrast videomicroscopy and immunomorphological analysis. The final stage of apoptosis accompanied by cell rounding and general blebbing of the cell surface became after 4–6 h of incubation but much earlier, after 1.5–3 h, essentially flattened lamellipodia at the active edges transformed into the small blebs that were continuously extended and retracted during the next 1–2 h. This phenomenon was called “marginal blebbing”. It took place before the cytochrome c release from mitochondria to cytosol. Marginal blebbing was inhibited by drugs that depolymerized actin microfilaments (cytochalasin, latrunculin) or decreased Rho‐kinase‐dependent contractility of actin—myosin cortex (H7, HA‐1077, Y27632). A pancaspase inhibitor, zVAD‐fmk, completely prevented marginal and general blebbing, and TNF‐induced apoptosis. DEVD‐fmk, a specific inhibitor of caspase‐3, inhibited both marginal and general blebbing but not cell rounding and death. Thus, marginal blebbing is an early microfilament‐dependent apoptotic event. It is suggested that it is initiated by minimal activation of caspase‐3 and the following local Rho‐kinase‐dependent stimulation of actin—myosin cortex contractility. Localization of marginal blebs at the active edge may be associated with special organization of cortex in that zone.