Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support

Authors

  • S. Celeste Morley,

    1. Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
    2. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
    3. Committee on Immunology, Division of Medical Sciences, Boston, Massachusetts 02115
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  • Guang-Ping Sun,

    1. Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
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  • Barbara E. Bierer

    Corresponding author
    1. Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
    2. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115
    3. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115
    • Dana 810, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.
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  • This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259–4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, a well-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-xL, but, unlike jasplakinolide, cytochalasin D modestly affected the “execution” stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway. J. Cell. Biochem. 88: 1066–1076, 2003. Published 2003 Wiley-Liss, Inc.

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