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Abstract
Activated T cells require anti-apoptotic cytokines for their survival. The anti-apoptotic effects of these factors are mediated by their influence on the balance of expression and localisation of pro- and anti-apoptotic members of the Bcl-2 family. Among the anti-apoptotic Bcl-2 family members, the expression level of Bcl-2 itself and its interaction with the pro-apoptotic protein Bim are now regarded as crucial for the regulation of survival in activated T cells. We studied the changes in Bcl-2 levels and its subcellular distribution in relation to mitochondrial depolarisation and caspase activation in survival factor deprived T cells. Intriguingly, the total Bcl-2 level appeared to remain stable, even after caspase 3 activation indicated entry into the execution phase of apoptosis. However, cell fractionation experiments showed that while the dominant nuclear pool of Bcl-2 remained stable during apoptosis, the level of the smaller mitochondrial pool was rapidly downregulated. Signals induced by anti-apoptotic cytokines continuously replenish the mitochondrial pool, but nuclear Bcl-2 is independent of such signals. Mitochondrial Bcl-2 is lost rapidly by a caspase independent mechanism in the absence of survival factors, in contrast only a small proportion of the nuclear pool of Bcl-2 is lost during the execution phase and this loss is a caspase dependent process. We conclude that these two intracellular pools of Bcl-2 are regulated through different mechanisms and only the cytokine-mediated regulation of the mitochondrial pool is relevant to the control of the initiation of apoptosis.
Original language | English |
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Pages (from-to) | 109-17 |
Number of pages | 9 |
Journal | Apoptosis |
Volume | 23 |
Issue number | 1 |
Early online date | 23 Oct 2007 |
DOIs | |
Publication status | Published - 1 Jan 2008 |
Keywords
- cytokines
- lymphocytes
- programmed cell death
- Bcl-2
- survival
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Dive into the research topics of 'Differential regulation of nuclear and mitochondrial Bcl-2 in T cell apoptosis'. Together they form a unique fingerprint.Projects
- 1 Finished
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The Role of Fibroblasts in the Regulation of Leucocyte Retention in Chronic Inflammation
Buckley, C.
1/10/01 → 30/09/06
Project: Research Councils