TAILIEUCHUNG - Báo cáo khoa học: Regulation of the expression and subcellular localization of the taurine transporter TauT in mouse NIH3T3 fibroblasts

The cellular level of the organic osmolyte taurine is abalance betweenactiveuptakeandpassive leakviaavolume sensitive pathway. Here, we demonstrate that NIH3T3 mouse fibro-blasts express a saturable, high affinity taurine transporter (TauT,Km¼18lM), and that taurine uptake via TauT is aNa+ -and Cl– -dependent process with an apparent : 1 : 1 Na + /Cl – /taurine stoichiometry. Transport activ-ity is reduced following acute administration of H2O2 or activatorsof proteinkinasesAorC. | Eur. J. Biochem. 271 4646-4658 2004 FEBS 2004 doi Regulation of the expression and subcellular localization of the taurine transporter TauT in mouse NIH3T3 fibroblasts Jesper W. Voss Stine F. Pedersen Soren T. Christensen and Ian H. Lambert The August Krogh Institute Biochemical Department Universitetsparken 13 Copenhagen Denmark The cellular level of the organic osmolyte taurine is a balance between active uptake and passive leak via a volume sensitive pathway. Here we demonstrate that NIH3T3 mouse fibroblasts express a saturable high affinity taurine transporter TauT Km 18 M and that taurine uptake via TauT is a Na - and Cl--dependent process with an apparent 1 1 Na Cl- taurine stoichiometry. Transport activity is reduced following acute administration of H2O2 or activators of protein kinases A or C. TauT transport activity expression and nuclear localization are significantly increased upon serum starvation 24 h exposure to tumour necrosis factor alpha TNFa 16 h or hyperosmotic medium 24 h conditions that are also associated with increased localization of TauT to the cytosolic network of microtubules. Conversely transport activity expression and nuclear localization of TauT are reduced in a reversible manner following long-term exposure 24 h to high extracellular taurine concentration. In contrast to active taurine uptake swelling-induced taurine release is significantly reduced following preincubation with TNFa 16 h but unaffected by high extracellular taurine concentration 24 h . Thus in NIH3T3 cells a active taurine uptake reflects TauT expression b TauT activity is modulated by multiple stimuli both acutely and at the level of TauT expression c the subcellular localization of TauT is regulated and d volume-sensitive taurine release is not mediated by TauT. Keywords TNFa creatine microtubules reactive oxygen species volume-sensitive taurine leak pathway. Taurine amino ethane sulfonic acid plays an essential role not only .

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