Cooperative Control of Akt Phosphorylation, bcl-2 Expression, and Apoptosis by Cytoskeletal Microfilaments and Microtubules in Capillary Endothelial Cells
- 1 October 2001
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 12 (10), 3087-3094
- https://doi.org/10.1091/mbc.12.10.3087
Abstract
Capillary endothelial cells can be switched between growth and apoptosis by modulating their shape with the use of micropatterned adhesive islands. The present study was carried out to examine whether cytoskeletal filaments contribute to this response. Disruption of microfilaments or microtubules with the use of cytochalasin D or nocodazole, respectively, led to levels of apoptosis in capillary cells equivalent to that previously demonstrated by inducing cell rounding with the use of micropatterned culture surfaces containing small (<20 microm in diameter) circular adhesive islands coated with fibronectin. Simultaneous disruption of microfilaments and microtubules led to more pronounced cell rounding and to enhanced levels of apoptosis approaching that observed during anoikis in fully detached (suspended) cells, indicating that these two cytoskeletal filament systems can cooperate to promote cell survival. Western blot analysis revealed that the protein kinase Akt, which is known to be critical for control of cell survival became dephosphorylated during cell rounding induced by disruption of the cytoskeleton, and that this was accompanied by a decrease in bcl-2 expression as well as a subsequent increase in caspase activation. This ability of the cytoskeleton to control capillary endothelial cell survival may be important for understanding the relationship among extracellular matrix turnover, cell shape changes, and apoptosis during angiogenesis inhibition.Keywords
This publication has 65 references indexed in Scilit:
- The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assemblyCell Death & Differentiation, 2000
- The β4 Integrin Subunit Rescues A431 Cells from Apoptosis through a PI3K/Akt Kinase Signaling PathwayBiochemical and Biophysical Research Communications, 1999
- Intracellular Movement of Green Fluorescent Protein–Tagged Phosphatidylinositol 3-Kinase in Response to Growth Factor Receptor SignalingThe Journal of cell biology, 1999
- Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTENCell, 1998
- Stress-induced fractal rearrangement of the endothelial cell cytoskeleton causes apoptosisSurgery, 1998
- Proteases to die forGenes & Development, 1998
- The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of ApoptosisScience, 1997
- Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis.JCI Insight, 1996
- Cell shape, cytoskeletal mechanics, and cell cycle control in angiogenesisJournal of Biomechanics, 1995
- Disruption of epithelial cell-matrix interactions induces apoptosisThe Journal of cell biology, 1994