Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule

Carregando...
Imagem de Miniatura
Citações na Scopus
27
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
KARGER
Autores
QUEIROZ-LEITE, Gabriella D.
BEZERRA, Camila N. A.
REBOUCAS, Nancy Amaral
MALNIC, Gerhard
Citação
KIDNEY & BLOOD PRESSURE RESEARCH, v.36, n.1, p.320-334, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background/Aims: Fructose causes a sodium-sensitive hypertension and acutely reduces the urinary Na+ excretion, suggesting that it may regulate the activity of renal tubular sodium transporters. NHE3 is highly expressed in proximal tubule (PT), along with proteins that mediate fructose transport and metabolism. The present work was outlined to investigate whether fructose modulates proximal NHE3 activity and to elucidate the molecular mechanisms underlying this modulation. Methods/Results: Using in vivo stationary microperfusion, we observed that fructose stimulates NHE3 mediated JHCO(3)(-) reabsorption. The MAPK pathway is not involved in this activation, as demonstrated by using of MEK/MAPK inhibitors, whereas experiments using a PKA inhibitor suggest that PKA inhibition plays a role in this response. These results were confirmed in vitro by measuring the cell pH recovery rate after NH4Cl pulse in LLC-PK1, a pig PT cell line, which showed reduced cAMP levels and NHE3 phosphorylation at serine-552 (PKA consensus site) after fructose treatment. Conclusions: NHE3 activity is stimulated by fructose, which increases proximal tubule Na+ reabsorption. The molecular mechanisms involved in this process are mediated, at least in part, by downregulation of the PKA signaling pathway. Future studies are needed to address whether fructose-stimulated NHE3 activity may contribute to renal injury and hypertension.
Palavras-chave
Fructose, In situ microperfusion, cAMP, Sodium hydrogen exchangers, LLC-PK1 cells
Referências
  1. Basciano H., 2005, NUTR METAB, V2, P5, DOI 10.1186/1743-7075-2-5
  2. Biemesderfer D, 1997, AM J PHYSIOL-RENAL, V273, pF289
  3. BOYARSKY G, 1988, AM J PHYSIOL, V255, pC844
  4. Brown CM, 2008, AM J PHYSIOL-REG I, V294, pR730, DOI 10.1152/ajpregu.00680.2007
  5. Carraro-Lacroix LR, 2009, AM J PHYSIOL-RENAL, V297, pF1647, DOI 10.1152/ajprenal.00082.2009
  6. Carraro-Lacroix LR, 2006, AM J PHYSIOL-RENAL, V291, pF129, DOI 10.1152/ajprenal.00290.2005
  7. Catena C, 2003, KIDNEY INT, V64, P2163, DOI 10.1046/j.1523-1755.2003.00313.x
  8. Chen J, 2004, ANN INTERN MED, V140, P167
  9. Cirillo P, 2009, J AM SOC NEPHROL, V20, P545, DOI 10.1681/ASN.2008060576
  10. Crajoinas RO, 2010, AM J PHYSIOL-RENAL, V299, pF872, DOI 10.1152/ajprenal.00654.2009
  11. Davies SP, 2000, BIOCHEM J, V351, P95, DOI 10.1042/0264-6021:3510095
  12. De Mello AM, 1990, AM J PHYSIOL, V259, pF357
  13. Di SF, 2011, AM J PHYSIOL-CELL PH, V301, pC1290
  14. Diggle CP, 2009, J HISTOCHEM CYTOCHEM, V57, P763, DOI 10.1369/jhc.2009.953190
  15. Douard V, 2008, AM J PHYSIOL-ENDOC M, V295, pE227, DOI 10.1152/ajpendo.90245.2008
  16. Elliott SS, 2002, AM J CLIN NUTR, V76, P911
  17. Ferder L, 2010, CURR HYPERTENS REP, V12, P105, DOI 10.1007/s11906-010-0097-3
  18. Gersch MS, 2007, AM J PHYSIOL-RENAL, V293, pF1256, DOI 10.1152/ajprenal.00181.2007
  19. Girardi ACC, 2004, AM J PHYSIOL-CELL PH, V287, pC1238, DOI 10.1152/ajpcell.00186.2004
  20. Girardi ACC, 2012, AM J PHYSIOL-CELL PH, V302, pC1569, DOI 10.1152/ajpcell.00017.2012
  21. Gurley SB, 2011, CELL METAB, V13, P469, DOI 10.1016/j.cmet.2011.03.001
  22. Horita S, 2011, INT J HYPERTENS, V2011
  23. HWANG IS, 1987, HYPERTENSION, V10, P512
  24. Johnson RJ, 2010, J AM SOC NEPHROL, V21, P2036, DOI 10.1681/ASN.2010050506
  25. Johnson RJ, 2007, AM J CLIN NUTR, V86, P899
  26. Kocinsky HS, 2007, AM J PHYSIOL-RENAL, V293, pF212, DOI 10.1152/ajprenal.00042.2007
  27. Kocinsky HS, 2005, AM J PHYSIOL-RENAL, V289, pF249, DOI 10.1152/ajprenal.00082.2004
  28. Kurashima K, 1997, J BIOL CHEM, V272, P28672, DOI 10.1074/jbc.272.45.28672
  29. Le KA, 2009, AM J CLIN NUTR, V89, P1760, DOI 10.3945/ajcn.2008.27336
  30. Lessa LMA, 2009, REGUL PEPTIDES, V157, P37, DOI 10.1016/j.regpep.2009.06.005
  31. LOWRY OH, 1951, J BIOL CHEM, V193, P265
  32. Manolescu AR, 2007, PHYSIOLOGY, V22, P234, DOI 10.1152/physiol.00011.2007
  33. MAYES PA, 1993, AM J CLIN NUTR, V58, pS754
  34. Meneton P, 2005, PHYSIOL REV, V85, P679, DOI 10.1152/physrev.00056.2003
  35. MOE OW, 1995, J CLIN INVEST, V96, P2187, DOI 10.1172/JCI118273
  36. Nakayama T, 2010, AM J PHYSIOL-RENAL, V298, pF712, DOI 10.1152/ajprenal.00433.2009
  37. REILLY RF, 1991, AM J PHYSIOL, V261, pF1088
  38. Sanchez-Lozada LG, 2007, AM J PHYSIOL-RENAL, V292, pF423, DOI 10.1152/ajprenal.00124.2006
  39. Schwark JR, 1998, PFLUG ARCH EUR J PHY, V436, P797, DOI 10.1007/s004240050704
  40. Shoham DA, 2008, PLOS ONE, V3, DOI 10.1371/journal.pone.0003431
  41. Shugrue CA, 1999, J AM SOC NEPHROL, V10, P1649
  42. Singh AK, 2008, KIDNEY INT, V74, P438, DOI 10.1038/ki.2008.184
  43. Soleimani M, 2011, INT J NEPHROL, V2011
  44. Soleimani M, 2011, ACTA PHYSIOL, V201, P55, DOI 10.1111/j.1748-1716.2010.02167.x
  45. Stanhope KL, 2009, J CLIN INVEST, V119, P1322, DOI 10.1172/JCI37385
  46. Tappy L, 2010, PHYSIOL REV, V90, P23, DOI 10.1152/physrev.00019.2009
  47. Tran LT, 2009, MOL CELL BIOCHEM, V332, P145, DOI 10.1007/s11010-009-0184-4
  48. ULATE G, 1993, BRAZ J MED BIOL RES, V26, P773
  49. Wakabayashi S, 1997, PHYSIOL REV, V77, P51
  50. Wang T, 2001, AM J PHYSIOL-RENAL, V281, pF1117
  51. WEINTRAUB WH, 1989, AM J PHYSIOL, V257, pG317
  52. Zhao H, 1999, J BIOL CHEM, V274, P3978, DOI 10.1074/jbc.274.7.3978