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

Cell Biology International
Lidia V DomninaJury M Vasiliev

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-dep...Continue Reading

Citations

Mar 10, 2007·Archivum Immunologiae Et Therapiae Experimentalis·Jianjian Shi, Lei Wei
Nov 28, 2012·Apoptosis : an International Journal on Programmed Cell Death·Syam Prakash SomasekharanJean-Claude Martinou
Jan 12, 2008·The Journal of Biological Chemistry·Carl D BortnerJohn A Cidlowski
May 17, 2008·Pharmacological Reviews·Dolores D MrukC Yan Cheng
Jul 11, 2006·Biochimica Et Biophysica Acta·O Yu PletjushkinaV P Skulachev
Mar 23, 2017·Biochemistry. Biokhimii︠a︡·N P SudakovYu M Konstantinov
Dec 16, 2011·Oncotarget·Luca D'Agostino, Antonio Giordano
Jan 1, 2011·Expert Review of Ophthalmology·Kenneth J MandellBarbara Wirostko
Jun 6, 2009·Journal of Cell Science·Sam J MathewMaria Leptin

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