Alteration of glutathione (GSH) homeostasis represents one of the earliest events during the commitment of stress-induced apoptosis. Extrusion of GSH into the extracellular milieu, in response to several oxidative stimuli, has been suggested as a molecular switch triggering apoptosis. However, chemical depletion of GSH does not induce cell death even though cytochrome c release from mitochondria has been observed. Here we report that U937 cells treated with buthionine sulfoximine (BSO) are able to survive and to inhibit the apoptotic program downstream of cytochrome c release. BSO treatment induces a highly significant decrease of GSH in both the cytosolic and mitochondrial fractions. The concomitant release of cytochrome c into the cytosol was associated with nuclear translocation of apoptosis-inducing factor. GSH depletion also resulted in reactive oxygen species production and in a specific increase of mitochondrial protein carbonyls. However, all these events were transiently present inside cells and efficiently counteracted by cell-repairing systems. We observed an increase in the proteasome activity and in the expression levels of heat shock protein 27 (Hsp27) and Hsp70. Moreover, nuclear factor-kappaB (NF-kappaB) was activated in our system as a survival cell response against the oxidative injury. Overall results suggest that activation of NF-kappaB and Hsp could allow cell adaptation and survival under exhaustive GSH depletion.

Filomeni, G., Aquilano, K., Rotilio, G., & Ciriolo, M.R. (2005). Antiapoptotic response to induced GSH depletion: Involvement of heat shock proteins and NF-kappa B activation. ANTIOXIDANTS & REDOX SIGNALING, 7(2009/04/03 00:00:00.000), 446-455 [10.1089/ars.2005.7.446].

Antiapoptotic response to induced GSH depletion: Involvement of heat shock proteins and NF-kappa B activation

FILOMENI, GIUSEPPE;AQUILANO, KATIA;ROTILIO, GIUSEPPE;CIRIOLO, MARIA ROSA
2005

Abstract

Alteration of glutathione (GSH) homeostasis represents one of the earliest events during the commitment of stress-induced apoptosis. Extrusion of GSH into the extracellular milieu, in response to several oxidative stimuli, has been suggested as a molecular switch triggering apoptosis. However, chemical depletion of GSH does not induce cell death even though cytochrome c release from mitochondria has been observed. Here we report that U937 cells treated with buthionine sulfoximine (BSO) are able to survive and to inhibit the apoptotic program downstream of cytochrome c release. BSO treatment induces a highly significant decrease of GSH in both the cytosolic and mitochondrial fractions. The concomitant release of cytochrome c into the cytosol was associated with nuclear translocation of apoptosis-inducing factor. GSH depletion also resulted in reactive oxygen species production and in a specific increase of mitochondrial protein carbonyls. However, all these events were transiently present inside cells and efficiently counteracted by cell-repairing systems. We observed an increase in the proteasome activity and in the expression levels of heat shock protein 27 (Hsp27) and Hsp70. Moreover, nuclear factor-kappaB (NF-kappaB) was activated in our system as a survival cell response against the oxidative injury. Overall results suggest that activation of NF-kappaB and Hsp could allow cell adaptation and survival under exhaustive GSH depletion.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10
English
Con Impact Factor ISI
apoptosis inducing factor; buthionine sulfoximine; carbonyl derivative; cytochrome c; glutathione; heat shock protein 27; heat shock protein 70; immunoglobulin enhancer binding protein; mitochondrial protein; proteasome; reactive oxygen metabolite; adaptation; apoptosis; article; cell survival; controlled study; cytosol; human; human cell; monocytic leukemia; oxidative stress; priority journal; protein depletion; protein expression; protein secretion; Apoptosis; Apoptosis Inducing Factor; Buthionine Sulfoximine; Cytochromes c; Flavoproteins; Glutathione; Heat-Shock Proteins; Humans; Membrane Proteins; Mitochondria; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; U937 Cells
Filomeni, G., Aquilano, K., Rotilio, G., & Ciriolo, M.R. (2005). Antiapoptotic response to induced GSH depletion: Involvement of heat shock proteins and NF-kappa B activation. ANTIOXIDANTS & REDOX SIGNALING, 7(2009/04/03 00:00:00.000), 446-455 [10.1089/ars.2005.7.446].
Filomeni, G; Aquilano, K; Rotilio, G; Ciriolo, Mr
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/38359
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