title: Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts.
abstract: The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na(+) concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.
authors.affiliation: Department of Biology, Section of Cellular and Developmental Biology, University of Copenhagen, The August Krogh Building, Universitetsparken 13, 2100 Copenhagen Ø, Denmark.
authors.forename: Daniel Bloch
authors.initials: DB
authors.lastname: Hansen
authors.forename: Martin Barfred
authors.initials: MB
authors.lastname: Friis
authors.forename: Else Kay
authors.initials: EK
authors.lastname: Hoffmann
authors.forename: Ian Henry
authors.initials: IH
authors.lastname: Lambert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D009995:Osmosis; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D013654:Taurine / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014882:Water-Electrolyte Balance; D000099247:Taurine Transporters
chemical_list: D006861:Hydrogen Peroxide; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012964:Sodium; D013654:Taurine; D014157:Transcription Factors; D000099247:Taurine Transporters; C492200:Nfat5 protein, mouse; C422943:Nox4 protein, mouse