UCP4 is a target effector of the NF-κB c-Rel prosurvival pathway against oxidative stress.

Free Radical Biology & Medicine
Jessica Wing-Man HoShu-Leong Ho

Abstract

Mitochondrial uncoupling protein-4 (UCP4) enhances neuronal survival in 1-methyl-4-phenylpyridinium (MPP(+)) toxicity by suppressing oxidative stress and preserving intracellular ATP and mitochondrial membrane potential (MMP). NF-κB regulates neuronal viability via its complexes, p65 mediating cell death and c-Rel promoting cell survival. We reported previously that NF-κB mediates UCP4 neuroprotection against MPP(+) toxicity. Here, we investigated its link with the NF-κB c-Rel prosurvival pathway in alleviating mitochondrial dysfunction and oxidative stress. We overexpressed a c-Rel-encoding plasmid in SH-SY5Y cells and showed that c-Rel overexpression induced NF-κB activity without affecting p65 level. Overexpression of c-Rel increased UCP4 promoter activity and protein expression. Electrophoretic mobility shift assay showed that H(2)O(2) increased NF-κB binding to the UCP4 promoter and that NF-κB complexes were composed of p50/p50 and p50/c-Rel dimers. Under H(2)O(2)-induced oxidative stress, UCP4 knockdown significantly increased superoxide levels, decreased reduced glutathione (GSH) levels, and increased oxidized glutathione levels, compared to controls. UCP4 expression induced by c-Rel overexpression significantly decrease...Continue Reading

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Citations

Aug 24, 2012·Brain : a Journal of Neurology·Cristina BaigueraMarina Pizzi
Sep 15, 2014·Journal of Bioenergetics and Biomembranes·Susana CardosoPaula I Moreira
Jan 21, 2018·Antioxidants & Redox Signaling·Petr JežekMartin Jabůrek
Aug 26, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kai WuTao Wang
May 30, 2019·Translational Neurodegeneration·Edoardo ParrellaMarina Pizzi
May 6, 2019·Journal of Bioenergetics and Biomembranes·Ludmila P DolgachevaAndrey Y Abramov
Sep 7, 2017·Neurotoxicity Research·Susana CardosoPaula I Moreira
Jun 27, 2013·Alcoholism, Clinical and Experimental Research·Jan A GrawClaudia D Spies
Feb 23, 2021·Journal of Neurochemistry·Dennison TrinhJoanne E Nash
Jun 6, 2017·Neurochemistry International·Scott J Koppel, Russell H Swerdlow

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