title: HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox.
abstract: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase catalyzes the transfer of electrons from NADPH to O2, which is the main source of reactive oxygen species (ROS) in nonphagocytic cells. Excess ROS are toxic; therefore, keeping ROS in homeostasis in cells can protect cells from oxidative damage. It is meaningful to further understand the molecular mechanism by which ROS homeostasis is mediated. Human protein HSCARG is a newly identified oxidative sensor and a negative regulator of NF-κB. Here, we find that HSCARG represses the cellular ROS generation through inhibiting mRNA and protein expression of p47phox, a subunit of NADPH oxidase. In contrast, shRNA-mediated HSCARG knockdown increases endogenous p47phox expression level. And HSCARG has no obvious effect on ROS production in p47phox-depleted cells. Furthermore, HSCARG regulates p47phox through inhibition of NF-κB activity. Our findings identify HSCARG as a novel regulator in regulation of the activity of NADPH oxidase and ROS homeostasis.
authors.affiliation: State Key Lab of Protein and Plant Gene Research, Beijing, China.
authors.forename: Weichun
authors.initials: W
authors.lastname: Xiao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008156:Luciferases; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; C520476:NMRAL1 protein, human; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D008156:Luciferases; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1