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.

Cristofanon, S. (2008). Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB.

Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB

CRISTOFANON, SILVIA
2008-08-26

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.
26-ago-2008
A.A. 2007/2008
Biologia molecolare e cellulare
20.
GSH; Bcl-3; Bcl-2; NF-kappaB; oxidative stress
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Tesi di dottorato
Cristofanon, S. (2008). Pathways of survival to oxidative stress: competition between Bcl-2 and Bax and role of NF-kappaB.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/583
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