title: Involvement of NADPH oxidase in up-regulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts induced by oxidized LDL and in apolipoprotein E-deficient mice.
abstract: The present study demonstrated that oxidized LDL (oLDL) increased the generation of superoxide and hydrogen peroxide (H(2)O(2)), the abundances of NADPH oxidase (NOX)4, NOX2, p22-phox and lectin-like oLDL receptor-1 (LOX-1) in wild-type or heat shock factor-1 (HSF1)-deficient mouse embryo fibroblasts (MEF). LOX-1 antibody inhibited LDL or oLDL-induced expression of NOX components in MEF. Abundance of HSF1 or plasminogen activator inhibitor-1 (PAI-1) was increased by oLDL in wild-type, but not in HSF1-deficient MEF. Diphenyleneiodonium or siRNA for NOX or p22-phox inhibited oLDL-induced increases of HSF1, PAI-1 and H(2)O(2) in MEF. Increased NOX4, NOX2, LOX1, HSF1 and PAI-1 were detected in aortae and hearts of apolipoprotein E-knockout (apoE-KO) mice compared to controls, which were associated with increased serum cholesterol or plasma PAI-1. The results suggest that NOX is required for oLDL-induced HSF1 or PAI-1 expression in MEF, which was supported by the up-regulation of NOX, LOX-1, HSF1 and PAI-1 in apoE-KO mice.
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Ruozhi
authors.initials: R
authors.lastname: Zhao
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Moghadasian
authors.forename: Garry X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D000076249:Heat Shock Transcription Factors; D006861:Hydrogen Peroxide / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D058258:Serpin E2 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; C495138:Olr1 protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; D013481:Superoxides; D006861:Hydrogen Peroxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse