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Please use this identifier to cite or link to this item: http://hdl.handle.net/2108/583

Title: Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB
Authors: Ghibelli, Lina
Diederich, Marc
Cristofanon, Silvia
Keywords: GSH
Bcl-2
NF-kappaB
oxidative stress
Bcl-3
Issue Date: 26-Aug-2008
Abstract: Buthionine Sulfoximine (BSO) is a well-known inhibitor of glutathione synthesis, producing slow glutathione depletion and oxidative stress; some “responder” cells avoid BSO-induced death by trans-activating the pro-survival protein Bcl-2. Here we show that BSO activates a non-canonical, IκB- and p65-independent NFκB pathway, via a multi-step process leading to the up-regulation of Bcl-2. The slow BSO-induced GSH depletion allows separating two redox-related phases, namely, early thiol disequilibrium, and late frank oxidative stress; each phase contributes to the progressive activation of a p50-p50 homo-dimer. The early phase, coinciding with substantial thiol depletion, produces a cytosolic preparative complex, consisting of p50 and its inter-actor Bcl-3 linked by inter-protein disulfide bridges. The late phase, coinciding with ROS production, is responsible, probably via p38 activation, of nuclear targeting of the complex, and trans-activation of Bcl-2.
Description: 20. ciclo
URI: http://hdl.handle.net/2108/583
Appears in Collections:Tesi di dottorato in scienze matematiche e fisiche

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