Loss of the transcriptional repressor Rev-erbα upregulates metabolism and proliferation in cultured mouse embryonic fibroblasts.

Scientific Reports
Sean P GillisPhyllis A Dennery

Abstract

The transcriptional repressor Rev-erbα is known to down-regulate fatty acid metabolism and gluconeogenesis gene expression. In animal models, disruption of Rev-erbα results in global changes in exercise performance, oxidative capacity, and blood glucose levels. However, the complete extent to which Rev-erbα-mediated transcriptional repression of metabolism impacts cell function remains unknown. We hypothesized that loss of Rev-erbα in a mouse embryonic fibroblast (MEF) model would result in global changes in metabolism. MEFs lacking Rev-erbα exhibited a hypermetabolic phenotype, demonstrating increased levels of glycolysis and oxidative phosphorylation. Rev-erbα deletion increased expression of hexokinase II, transketolase, and ribose-5-phosphate isomerase genes involved in glycolysis and the pentose phosphate pathway (PPP), and these effects were not mediated by the transcriptional activator BMAL1. Upregulation of oxidative phosphorylation was not accompanied by an increase in mitochondrial biogenesis or numbers. Rev-erbα repressed proliferation via glycolysis, but not the PPP. When treated with H2O2, cell viability was reduced in Rev-erbα knockout MEFs, accompanied by increased ratio of oxidized/reduced NADPH, suggesting that...Continue Reading

References

Mar 10, 1977·The New England Journal of Medicine·G Weber
Sep 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·E Bustamante, P L Pedersen
Jul 30, 1990·FEBS Letters·T PopoviciH Skala
Jan 1, 1989·Chemico-biological Interactions·E G JanzenJ W Hilborn
Feb 1, 1974·Journal of Bacteriology·E M GregoryI Fridovich
Jan 28, 1982·Brain Research·R J ThompsonV J Willson
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·G F VileR M Tyrrell
Nov 28, 2002·Journal of Lipid Research·Eric RaspéBart Staels
Feb 24, 1956·Science·O WARBURG
Sep 4, 2007·FEBS Letters·Hélène Duez, Bart Staels
Jan 20, 2011·Magnetic Resonance in Chemistry : MRC·Kalina Ranguelova, Ronald P Mason
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Julie E GibbsAndrew S I Loudon
Apr 10, 2012·Annual Review of Neuroscience·Jennifer A MohawkJoseph S Takahashi
May 9, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Julien DelezieEtienne Challet
Jul 31, 2013·Experimental Hematology & Oncology·Jiarui WangGary Guishan Xiao
Jul 20, 2014·Trends in Biochemical Sciences·Krushna C Patra, Nissim Hay
Nov 29, 2014·International Journal of Cancer. Journal International Du Cancer·Shih-Ci CiouHorng-Dar Wang
Jun 11, 2017·Molecular and Cellular Endocrinology·Na-Lee KaMi-Ock Lee
Dec 15, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tianpeng ZhangBaojian Wu
Jun 26, 2018·Cell Metabolism·Miriam ToledoRajat Singh
Dec 21, 2018·American Journal of Respiratory Cell and Molecular Biology·Hongwei YaoPhyllis A Dennery
Dec 28, 2018·Cell Reports·Mohammed AmirLaura A Solt
Jan 15, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xue YuanBaojian Wu

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