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Verfaillie, T,van Vliet, A,Garg, AD,Dewaele, M,Rubio, N,Gupta, S,de Witte, P,Samali, A,Agostinis, P
Biochemical And Biophysical Research Communications
Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim
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Photodynamic therapy (PDT) Bladder cancer Hypericin Endoplasmic reticulum stress Bim Cell death Apoptosis PERK CELL-DEATH PHOTODYNAMIC THERAPY EXPOSURE PERK
Pro-apoptotic signaling instigated by endoplasmic reticulum (ER) stress is tightly governed by the BH3-only proteins like Noxa and Bim, which help trigger apoptosis, in part by inactivating mitochondria protecting proteins like Mcl-1. Bim/Noxa-based pro-apoptotic signaling has been implicated for various ER stressors but not yet for those causing "ER-focused" production of severe oxidative stress. In the present study we found that photo-oxidative (phox)-ER stress induced by hypericin-based photodynamic therapy is associated with activation of PERK (an ER sessile, stress sensor), robust induction of CHOP (a pro-apoptotic transcription factor) and induction of Bim and Noxa (accompanied by an eventual drop in Mcl-1 levels). Interestingly Noxa, but not Bim, contributed toward phox-ER stress induced apoptosis, regulated by PERK in a CHOP-independent, temporally-defined manner. These observations shed further light on complex signaling pathways elicited byphox-ER stress and vouch for directing more investigation toward the role of PERK in cell death governance. (C) 2013 Elsevier Inc. All rights reserved.
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