Reactive oxygen species regulate quiescent T-cell apoptosis via the BH3-only pro-apoptotic protein BIM

Sade, H. ; Sarin, A. (2004) Reactive oxygen species regulate quiescent T-cell apoptosis via the BH3-only pro-apoptotic protein BIM Cell Death and Differentiation, 11 . pp. 416-423. ISSN 1350-9047

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Official URL: http://www.nature.com/cdd/journal/v11/n4/abs/44013...

Related URL: http://dx.doi.org/10.1038/sj.cdd.4401347

Abstract

The survival of quiescent T cells in the peripheral immune system is dependent on signals transmitted from the extracellular environment. The requirement for survival factors is also manifested in vitro, providing a robust system to examine molecular mechanisms underlying T-cell death. We show that peripheral T cells cultured in the absence of survival factors accumulate reactive oxygen species (ROS), upregulate BIM (Bcl-2-interacting mediator of death) and inducible nitric oxide synthase (iNOS) expression, culminating in Fas-independent neglect-induced death (NID). We have examined ROS, iNOS and cytokine modulation of T-cell NID. Antioxidants inhibit BIM induction, caspase activation and apoptosis but do not promote cell cycle entry. iNOS-deficient T cells are protected from apoptosis, implicating iNOS in the regulation of NID via suppression of Bcl-xL expression and consequent inhibition of BIM activity. Finally, we show that the prosurvival cytokine IL-7 elevates Bcl-xL expression and transcriptionally regulates iNOS but not BIM expression in T cells.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:T Cells; Apoptosis; BIM; ROS; NOS
ID Code:62122
Deposited On:17 Sep 2011 11:43
Last Modified:17 Sep 2011 11:43

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