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J Membrane Biol (2012) 245:7787 DOI 10.1007/s00232-012-9416-8
Downregulation of the Taurine Transporter TauT During Hypo-Osmotic Stress in NIH3T3 Mouse Fibroblasts
Daniel Bloch Hansen Martin Barfred Friis
Else Kay Hoffmann Ian Henry Lambert
Received: 8 July 2011 / Accepted: 26 January 2012 / Published online: 2 March 2012 The Author(s) 2012. This article is published with open access at Springerlink.com
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 broblasts during acute and long-term (4 h) exposure to low-sodium/ hypo-osmotic stress. Taurine inux 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 signicantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are signicantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 broblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H2O2 or overexpressing NOX4, we demonstrate that TonEBP activity and taurine inux 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.
Keywords NADPH oxidase Hyponatremia
Osmolyte transport Hypo-osmolal
Introduction
The ability to restore cell volume following osmotic perturbation is pivotal for cell function, and we have recently reviewed the intracellular signaling events evoked by cell swelling and cell shrinkage, as well as the biophysical and pharmacological characteristics of volume-sensitive transporters for organic and inorganic osmolytes (Hoffmann et al. 2009; Lambert et al. 2008). Mammalian cells restore their cell volume following osmotic perturbation; i.e., KCl, organic osmolytes (amino acids/sugars), and water are released to or taken up from the extracellular compartment following cell swelling and cell shrinkage, respectively (Hoffmann et al. 2009). The organic acid taurine is quantitatively an important osmolyte in mammalian cells, and even though taurine is mainly recognized through its contribution to the cellular pool of organic osmolytes, it has in recent years turned out that taurine modulates multiple cellular functions through stabilization of membrane integrity, modulation...