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Slc14a2  -  solute carrier family 14 (urea...

Rattus norvegicus

Synonyms: Slc14a2T, Slc14a2_v4, Solute carrier family 14 member 2, UrT1-C, UrT1-D, ...
 
 
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Disease relevance of Slc14a2

  • We conclude that (1) multiple UT-A proteins are detected in rat and human heart; (2) the 56-kDa protein is upregulated in rat heart in uremia or models of hypertension; and (3) the rat results can be extended to human heart, where 56- and 51-kDa proteins are increased during heart failure [1].
  • We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure [1].
  • To determine whether acidosis alone would increase UT-A protein in liver, rats were made acidotic, but not uremic, by feeding them HCl [2].
  • BACKGROUND: The facilitated urea transporters (UT), UT-A1, UT-A2, and UT-B1, are involved in intrarenal recycling of urea, an essential feature of the urinary concentrating mechanism, which is impaired in chronic renal failure (CRF) [3].
  • These data suggest that (1) the previously reported effect of kidney medulla hypertonicity on UT-A2 and UT-B1 mRNA expression is somehow obliterated by protein intake deficiency or excess, and (2) AVP influences the mRNA abundance of the UT-A1 of the terminal IMCD during protein deficiency [4].
 

Psychiatry related information on Slc14a2

  • Our findings suggest that two promoters regulate transcription of the four UT-A isoforms, and that stimulation of transcription by vasopressin, mediated by cAMP and CRE sequences, and controlled by an intronic promoter, may contribute to the increase in UT-A2 expression during water deprivation [5].
 

High impact information on Slc14a2

 

Chemical compound and disease context of Slc14a2

 

Biological context of Slc14a2

 

Anatomical context of Slc14a2

  • UT-A3 and UT-A4 mRNA are expressed in the renal outer and inner medulla but not in the cortex; unidentified UT-A isoforms similar to UT-A3 may also be expressed in the testis [8].
  • We report the anatomic distribution of UrT1-C in the rat kidney tubule system as well as a detailed functional characterization [11].
  • When expressed in Xenopus laevis oocytes, UrT1-C induced a 15-fold stimulation of urea uptake, which was inhibited almost completely by phloretin (0.7 mM) and 60-95% by thiourea analogs (150 mM) [11].
  • In conclusion, reduced expression of UT-A1, UT-A3, and UT-B levels in both BUO and UUO rats suggests that urea transporters play important roles in the impaired urinary concentrating capacity in response to urinary tract obstruction [12].
  • UT-A2 immunoreactivity intensities in the plasma membrane and cytoplasm of type I, II, and III epithelia of DTL were greater in WD vs. controls [13].
 

Associations of Slc14a2 with chemical compounds

 

Other interactions of Slc14a2

  • UrT1-C has 70 and 62% amino acid identity to rat UrT1-B and UrT2 (UT3), respectively, and 99% identity to a recently reported rat isoform (UT-A3; Karakashian A, Timmer RT, Klein JD, Gunn RB, Sands JM, and Bagnasco SM. J Am Soc Nephrol 10: 230-237, 1999) [11].
  • UT-A proteins were detected in Sertoli cell nuclei at all stages of tubule development and in residual bodies of stage VIII tubules [16].
  • HCl-feeding significantly increased the abundance of the 117-kD UT-A1 protein in kidney inner medulla but did not change aquaporin-2 protein [2].
 

Analytical, diagnostic and therapeutic context of Slc14a2

  • Immunocytochemistry confirmed downregulation of UT-A1 and UT-A3 in IM collecting duct and UT-B in the descending vasa recta [12].
  • Electrophoretic mobility shift assay using the 5' UT-A TonE sequence as DNA probe showed formation of a specific DNA-protein complex with nuclear extracts from cells exposed to hypertonic medium and was weakly detectable in isotonic controls [6].
  • To determine whether the abundance of these UT-A proteins varies in vivo, rats were made uremic by 5/6 nephrectomy [17].
  • Immunoblotting showed complete disappearance of the 97 and 117 kD bands of UT-A1, and considerable reduction of UT-A2 and UT-B1 in the renal medulla [3].
  • Our results show that none of these transporters is affected by the level of protein intake, except UT-A1 that is reduced in terminal IMCD by low protein diet in the absence of AVP (Brattleboro rats) [4].

References

  1. UT-A urea transporter protein in heart: increased abundance during uremia, hypertension, and heart failure. Duchesne, R., Klein, J.D., Velotta, J.B., Doran, J.J., Rouillard, P., Roberts, B.R., McDonough, A.A., Sands, J.M. Circ. Res. (2001) [Pubmed]
  2. Acidosis mediates the upregulation of UT-A protein in livers from uremic rats. Klein, J.D., Rouillard, P., Roberts, B.R., Sands, J.M. J. Am. Soc. Nephrol. (2002) [Pubmed]
  3. Massive reduction of urea transporters in remnant kidney and brain of uremic rats. Hu, M.C., Bankir, L., Michelet, S., Rousselet, G., Trinh-Trang-Tan, M.M. Kidney Int. (2000) [Pubmed]
  4. mRNA expression of renal urea transporters in normal and Brattleboro rats: effect of dietary protein intake. Hu, M.C., Bankir, L., Trinh-Trang-Tan, M.M. Exp. Nephrol. (1999) [Pubmed]
  5. Cloning of the rat Slc14a2 gene and genomic organization of the UT-A urea transporter. Nakayama, Y., Naruse, M., Karakashian, A., Peng, T., Sands, J.M., Bagnasco, S.M. Biochim. Biophys. Acta (2001) [Pubmed]
  6. The TonE/TonEBP pathway mediates tonicity-responsive regulation of UT-A urea transporter expression. Nakayama, Y., Peng, T., Sands, J.M., Bagnasco, S.M. J. Biol. Chem. (2000) [Pubmed]
  7. Molecular mechanisms of impaired urinary concentrating ability in glucocorticoid-deficient rats. Chen, Y.C., Cadnapaphornchai, M.A., Summer, S.N., Falk, S., Li, C., Wang, W., Schrier, R.W. J. Am. Soc. Nephrol. (2005) [Pubmed]
  8. Cloning and characterization of two new isoforms of the rat kidney urea transporter: UT-A3 and UT-A4. Karakashian, A., Timmer, R.T., Klein, J.D., Gunn, R.B., Sands, J.M., Bagnasco, S.M. J. Am. Soc. Nephrol. (1999) [Pubmed]
  9. Urea may regulate urea transporter protein abundance during osmotic diuresis. Kim, D., Klein, J.D., Racine, S., Murrell, B.P., Sands, J.M. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  10. Down-regulation of urea transporters in the renal inner medulla of lithium-fed rats. Klein, J.D., Gunn, R.B., Roberts, B.R., Sands, J.M. Kidney Int. (2002) [Pubmed]
  11. Molecular characterization of a novel urea transporter from kidney inner medullary collecting ducts. Shayakul, C., Tsukaguchi, H., Berger, U.V., Hediger, M.A. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  12. Altered expression of urea transporters in response to ureteral obstruction. Li, C., Klein, J.D., Wang, W., Knepper, M.A., Nielsen, S., Sands, J.M., Frøkiaer, J. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  13. Ultrastructural localization of UT-A and UT-B in rat kidneys with different hydration status. Lim, S.W., Han, K.H., Jung, J.Y., Kim, W.Y., Yang, C.W., Sands, J.M., Knepper, M.A., Madsen, K.M., Kim, J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  14. Aquaporin-2 and urea transporter-A1 are up-regulated in rats with type I diabetes mellitus. Bardoux, P., Ahloulay, M., Le Maout, S., Bankir, L., Trinh-Trang-Tan, M.M. Diabetologia (2001) [Pubmed]
  15. Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene. Peng, T., Sands, J.M., Bagnasco, S.M. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  16. Coordinated expression of UT-A and UT-B urea transporters in rat testis. Fenton, R.A., Cooper, G.J., Morris, I.D., Smith, C.P. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  17. UT-A urea transporter protein expressed in liver: upregulation by uremia. Klein, J.D., Timmer, R.T., Rouillard, P., Bailey, J.L., Sands, J.M. J. Am. Soc. Nephrol. (1999) [Pubmed]
 
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