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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

High Glucose Concentration Stimulates NHE-1 Activity in Distal Nephron Cells: the Role of the Mek/Erk1/2/p90(RSK) and p38MAPK Signaling Pathways

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Autor(es):
da Costa-Pessoa, Juliana Martins [1] ; Damasceno, Roselia Santos [1] ; Machado, Ubiratan Fabres [1] ; Beloto-Silva, Olivia [1] ; Oliveira-Souza, Maria [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 33, n. 2, p. 333-343, 2014.
Citações Web of Science: 8
Resumo

Aims: In models of diabetes, distal nephron cells contribute to glucose uptake and oxidation. How these cells contribute to the use of glucose for the regulation of H+ extrusion remains unknown. We used Madin-Darby Canine Kidney (MDCK) cells to investigate the effect of acute or chronic high glucose concentration on the abundance and activity of the Na+/H+ exchanger (NHE-1). Methods: Using RT-PCR, we also evaluated the mRNA expression for sodium glucose co-transporters SGLT1 and SGLT2. Protein abundance was analyzed using immunoblotting, and intracellular pH (pH(i)) recovery was evaluated using microscopy in conjunction with the fluorescent probe BCECF/AM. The Na+-dependent pHi recovery rate was monitored with HOE-694 (50 mu M) and/or S3226 (10 mu M), specific NHE-1 and NHE-3 inhibitors. Results: MDCK cells did not express the mRNA for SGLT1 or SGLT2 but did express the GLUT2, NHE-1 and NHE3 proteins. Under control conditions, we observed a greater contribution of NHE-1 to pHi recovery relative to the other H+ transporters. Acute high glucose treatment increased the HOE-694- sensitive pHi recovery rate and p-Erk1/2 and p90(RSK) abundance. These parameters were reduced by PD-98059, a Mek inhibitor (1 mu M). Chronic high glucose treatment also increased the HOE-694-sensitive pHi recovery rate and p-p38MAPK abundance. Both parameters were reduced by SB-203580, a p38MAPK inhibitor (10 mu M). Conclusion: These results suggested that extracellular high glucose stimulated NHE-1 acutely and chronically through Mek/Erk1/2/ p90(RSK) and p38MAPK pathways, respectively. Copyright (C) 2014 S. Karger AG, Basel (AU)

Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
Beneficiário:Ubiratan Fabres Machado
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 07/58966-7 - Analise da regulacao do ph intracelular em celulas renais.
Beneficiário:Maria Oliveira de Souza
Linha de fomento: Auxílio à Pesquisa - Regular