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EnglishAlteration 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.
| Tipologia: | Articolo su rivista |
| Citazione: | 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. |
| IF: | Con Impact Factor ISI |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore BIO/10 |
| Revisione (peer review): | Sì, ma tipo non specificato |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1089/ars.2005.7.446 |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 2005 |
| Titolo: | Antiapoptotic response to induced GSH depletion: Involvement of heat shock proteins and NF-kappa B activation |
| Autori: | |
| Autori: | Filomeni, G; Aquilano, K; Rotilio, G; Ciriolo, MR |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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