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Verfaillie T.,Laboratory of Cell Death Research and Therapy | van Vliet A.,Laboratory of Cell Death Research and Therapy | Garg A.D.,Laboratory of Cell Death Research and Therapy | Dewaele M.,Laboratory of Cell Death Research and Therapy | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

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. © 2013 Elsevier Inc. Source


Decuypere J.-P.,Catholic University of Leuven | Decuypere J.-P.,University Hospitals Leuven | Ceulemans L.J.,Catholic University of Leuven | Ceulemans L.J.,University Hospitals Leuven | And 9 more authors.
American Journal of Kidney Diseases | Year: 2015

Autophagy, an evolutionary conserved intracellular lysosome-dependent catabolic process, is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the kidney, such as ischemia-reperfusion injury (IRI). However, stimulation of autophagy has been described to both improve and exacerbate IRI in the kidney. We summarize the current understanding of autophagy in renal IRI and discuss possible reasons for these contradictory findings. Furthermore, we hypothesize that autophagy plays a dual role in renal IRI, having both protective and detrimental properties, depending on the duration of the ischemic period and the phase of the IRI process. Finally, we discuss the influence of currently used diuretics and immunosuppressive drugs on autophagy, underscoring the need to clarify the puzzling role of autophagy in renal IRI. © 2015 National Kidney Foundation, Inc. Source

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