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.
|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|
|Settore Scientifico Disciplinare:||Settore BIO/10|
|Revisione (peer review):||Sì, ma tipo non specificato|
|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:||Filomeni, G; Aquilano, K; Rotilio, G; Ciriolo, MR|
|Appare nelle tipologie:||01 - Articolo su rivista|