High Glucose Concentration Stimulates NHE-1 Activity in Distal Nephron Cells: the Role of the Mek/Erk1/2/p90RSKand p38MAPK Signaling Pathways
| Autor: | Olivia Beloto-Silva, Ubiratan Fabres Machado, Rosélia Santos Damasceno, Maria Oliveira-Souza, Juliana Martins Costa-Pessoa |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Sodium-Hydrogen Exchangers Physiology Intracellular pH Glucose uptake Sodium chemistry.chemical_element Ribosomal Protein S6 Kinases 90-kDa p38 Mitogen-Activated Protein Kinases lcsh:Physiology Madin Darby Canine Kidney Cells lcsh:Biochemistry Dogs Erk1/2 Internal medicine medicine Extracellular Animals lcsh:QD415-436 Kidney Tubules Distal NHE-1 Mitogen-Activated Protein Kinase 3 lcsh:QP1-981 biology MEK inhibitor MDCK cells Transporter Hydrogen-Ion Concentration MAP Kinase Kinase Kinases FISIOLOGIA Glucose Endocrinology chemistry Sweetening Agents p38MAPK biology.protein GLUT2 Signal transduction |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Cellular Physiology and Biochemistry, Vol 33, Iss 2, Pp 333-343 (2014) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000356673 |
| Popis: | 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 (pHi) 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 µM) and/or S3226 (10 µM), 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 NHE-3 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 p90RSK abundance. These parameters were reduced by PD-98059, a Mek inhibitor (1 µM). 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 µM). Conclusion: These results suggested that extracellular high glucose stimulated NHE-1 acutely and chronically through Mek/Erk1/2/p90RSK and p38MAPK pathways, respectively. |
| Databáze: | OpenAIRE |
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