Marginal blebbing during the early stages of TNF-induced apoptosis indicates alteration in actomyosin contractility.
Cell Biol Int
; 28(6): 471-5, 2004.
Article
em En
| MEDLINE
| ID: mdl-15223024
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Actomiosina
/
Membrana Celular
/
Fator de Necrose Tumoral alfa
/
Apoptose
Limite:
Humans
Idioma:
En
Revista:
Cell Biol Int
Ano de publicação:
2004
Tipo de documento:
Article