Fructose Acutely Stimulates NHE3 Activity in Kidney Proximal Tubule

Autor(es)

Queiroz-Leite, Gabriella D. ^[1] ; Crajoinas, Renato O. ^[2] ; Neri, Elida A. ^[1] ; Bezerra, Camila N. A. ^[1] ; Girardi, Adriana C. C. ^[2] ; Reboucas, Nancy Amaral ^[1] ; Malnic, Gerhard ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Kidney & Blood Pressure Research; v. 36, n. 1, p. 320-334, 2012.
• Citações Web of Science: 17

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. Copyright (C) 2012 S. Karger AG, Basel (AU)

• Processo FAPESP: 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular
• Beneficiário: Adriana Castello Costa Girardi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/04150-4 - A frutose como moduladora do transporte renal de H+
• Beneficiário: Gabriella Duarte Queiroz Leite
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/58287-5 - Estudo molecular e funcional de transportadores de ions em membranas
• Beneficiário: Gerhard Malnic
• Modalidade de apoio: Auxílio à Pesquisa - Temático