Regulation of the expression and subcellular localization of the taurine transporter TauT in mouse NIH3T3 fibroblasts

被引:53
作者
Voss, JW [1 ]
Pedersen, SF [1 ]
Christensen, ST [1 ]
Lambert, IH [1 ]
机构
[1] Univ Copenhagen, August Krogh Inst, Dept Biochem, DK-2100 Copenhagen, Denmark
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 2004年 / 271卷 / 23-24期
关键词
TNF alpha; creatine; microtubules; reactive oxygen species; volume-sensitive taurine leak pathway;
D O I
10.1111/j.1432-1033.2004.04420.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, K-m = 18 muM), and that taurine uptake via TauT is a Na+- and Cl--dependent process with an apparent 2.5 : 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 (TNFalpha; 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 TNFalpha (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.
引用
收藏
页码:4646 / 4658
页数:13
相关论文
共 43 条
[1]  
An HS, 2003, ADV EXP MED BIOL, V526, P131
[2]   Carrier-mediated uptake and release of taurine from Bergmann glia in rat cerebellar slices [J].
Barakat, L ;
Wang, D ;
Bordey, A .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 541 (03) :753-767
[3]  
Beckman ML, 1998, J MEMBRANE BIOL, V164, P1
[4]   Taurine down-regulates basal and osmolarity-induced gene expression of its transporter, but not the gene expression of its biosynthetic enzymes, in astrocyte primary cultures [J].
Bitoun, M ;
Tappaz, M .
JOURNAL OF NEUROCHEMISTRY, 2000, 75 (03) :919-924
[5]   Sequence and structure-based prediction of eukaryotic protein phosphorylation sites [J].
Blom, N ;
Gammeltoft, S ;
Brunak, S .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 294 (05) :1351-1362
[6]   Effects of tumor necrosis factor alpha on taurine uptake in cultured rat astrocytes [J].
Chang, RCC ;
Stadlin, A ;
Tsang, D .
NEUROCHEMISTRY INTERNATIONAL, 2001, 38 (03) :249-254
[7]   A regulatory light chain of ciliary outer arm dynein in Tetrahymena thermophila [J].
Christensen, ST ;
Guerra, C ;
Wada, Y ;
Valentin, T ;
Angeletti, RH ;
Satir, P ;
Hamasaki, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (23) :20048-20054
[8]   p53 Protects renal inner medullary cells from hypertonic stress by restricting DNA replication [J].
Dmitrieva, N ;
Michea, L ;
Burg, M .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2001, 281 (03) :F522-F530
[9]  
Han XB, 2003, ADV EXP MED BIOL, V526, P139
[10]   Transcriptional repression of taurine transporter gene (TauT) by p53 in renal cells [J].
Han, XB ;
Patters, AB ;
Chesney, RW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39266-39273