Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim

Tom Verfaillie; Alexander van Vliet; Abhishek D. Garg; Michael Dewaele; Noemi Rubio; Sanjeev Gupta; Peter de Witte; Afshin Samali; Patrizia Agostinis

doi:10.1016/j.bbrc.2013.07.107

Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim

Tom Verfaillie, Alexander van Vliet, Abhishek D. Garg, Michael Dewaele, Noemi Rubio, Sanjeev Gupta, Peter de Witte, Afshin Samali, Patrizia Agostinis

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

39 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	500-506
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	438
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2013.07.107
Publication status	Published - 30 Aug 2013

Keywords

Apoptosis
Bim
Bladder cancer
Cell death
Endoplasmic reticulum stress
Hypericin
PERK
Photodynamic therapy (PDT)

Authors (Note for portal: view the doc link for the full list of authors)

Authors
Verfaillie, T,van Vliet, A,Garg, AD,Dewaele, M,Rubio, N,Gupta, S,de Witte, P,Samali, A,Agostinis, P
Verfaillie T, van Vliet A, Garg AD, Dewaele M, Rubio N, Gupta S, de Witte P, Samali A, Agostinis P

UN SDGs

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10.1016/j.bbrc.2013.07.107

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title = "Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim",

abstract = "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.",

keywords = "Apoptosis, Bim, Bladder cancer, Cell death, Endoplasmic reticulum stress, Hypericin, PERK, Photodynamic therapy (PDT)",

author = "Tom Verfaillie and \{van Vliet\}, Alexander and Garg, \{Abhishek D.\} and Michael Dewaele and Noemi Rubio and Sanjeev Gupta and \{de Witte\}, Peter and Afshin Samali and Patrizia Agostinis",

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doi = "10.1016/j.bbrc.2013.07.107",

language = "English",

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AU - Verfaillie, Tom

AU - van Vliet, Alexander

AU - Garg, Abhishek D.

AU - Dewaele, Michael

AU - Rubio, Noemi

AU - Gupta, Sanjeev

AU - de Witte, Peter

AU - Samali, Afshin

AU - Agostinis, Patrizia

PY - 2013/8/30

Y1 - 2013/8/30

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bim

KW - Bladder cancer

KW - Cell death

KW - Endoplasmic reticulum stress

KW - Hypericin

KW - PERK

KW - Photodynamic therapy (PDT)

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DO - 10.1016/j.bbrc.2013.07.107

M3 - Article

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VL - 438

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Pro-apoptotic signaling induced by photo-oxidative ER stress is amplified by Noxa, not Bim

Abstract

Keywords

Authors (Note for portal: view the doc link for the full list of authors)

UN SDGs

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