Marginal blebbing during the early stages of TNF-induced apoptosis indicates alteration in actomyosin contractilityстатья

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[1] Marginal blebbing during the early stages of tnf-induced apoptosis indicates alteration in actomyosin contractility / L. V. Domnina, O. Y. Ivanova, O. Y. Pletjushkina et al. // Cell Biology International. — 2004. — Vol. 28, no. 6. — P. 471–475. 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 4-6h of incubation but much earlier, after 1.5-3h, essentially flattened lamellipodia at the active edges transformed into the small blebs that were continuously extended and retracted during the next 1-2h. 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. © 2004 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. [ DOI ]

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