Cloning of mesangial cell Na+/Ca2+exchangers from Dahl/Rapp salt-sensitive/resistant rats
| Autor: | János Peti-Peterdi, P. Darwin Bell, M. Tino Unlap |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Physiology Renal glomerulus Sodium Molecular Sequence Data Fluorescent Antibody Technique Renal function chemistry.chemical_element Calcium Transfection Sodium-Calcium Exchanger Internal medicine medicine Animals Protein Isoforms Amino Acid Sequence RNA Messenger Cloning Molecular Cells Cultured Protein Kinase C Kidney Rats Inbred Dahl Base Sequence Sodium-calcium exchanger Mesangial cell Glomerular Mesangium Rats Enzyme Activation Alternative Splicing Endocrinology medicine.anatomical_structure Blood pressure Gene Expression Regulation chemistry Hypertension Tetradecanoylphorbol Acetate |
| Zdroj: | American Journal of Physiology-Renal Physiology. 279:F177-F184 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.2000.279.1.f177 |
| Popis: | The Dahl/Rapp rat model of hypertension is characterized by a marked increase in blood pressure and a progressive fall in glomerular filtration rate when salt-sensitive (S) rats are placed on an 8% NaCl diet. On the same diet, the salt-resistant (R) rat does not exhibit these changes. In previous studies we found that protein kinase C (PKC) upregulates Na+/Ca2+exchanger activity in afferent arterioles and mesangial cells from R but not S rats. One possible reason for the difference in PKC sensitivity may be due to differences in the S and R Na+/Ca2+exchanger protein. We now report the cloning of Na+/Ca2+exchangers from R (RNCX1) and S (SNCX1) mesangial cells. At the amino acid level, SNCX1 differs from RNCX1 at position 218 in the NH2-terminal domain where it is isoleucine in RNCX1 but phenylalanine in SNCX1. These two exchangers also differ by 23 amino acids at the alternative splice site within the cytosolic domain. RNCX1 and SNCX1 were expressed in OK-PTH cells and45Ca2+-uptake studies were performed. Acute phorbol 12-myristate 13-acetate (PMA) treatment (300 nM, 20 min) upregulated exchanger activity in cells expressing RNCX1 but failed to stimulate exchanger activity in SNCX1 expressing cells. Upregulation of RNCX1 could be prevented by prior 24-h pretreatment with PMA, which downregulates PKC. These results demonstrate a difference in PKC-Na+/Ca2+exchange activity between the isoform of the exchanger cloned from the R vs. the S rat. Lack of PKC activation of SNCX1 may contribute to a dysregulation of intracellular Ca2+concentration and enhanced renal vasoreactivity in this model of hypertension. |
| Databáze: | OpenAIRE |
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