D 1 -Like Receptors Regulate NADPH Oxidase Activity and Subunit Expression in Lipid Raft Microdomains of Renal Proximal Tubule Cells
| Autor: | Van Anthony M. Villar, Mark T. Quinn, Hewang Li, Ulrich Hopfer, Lindsay B. Keever, Weixing Han, Quansheng Lu, Pedro A. Jose, Robin A. Felder, Peiying Yu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Luminescence Fenoldopam Immunoblotting Rats Inbred WKY Sensitivity and Specificity Article Kidney Tubules Proximal chemistry.chemical_compound Membrane Microdomains Rats Inbred SHR Internal medicine Internal Medicine medicine Animals RNA Messenger Receptor Lipid raft Cells Cultured Probability Analysis of Variance Oxidase test NADPH oxidase biology Cholesterol Receptors Dopamine D1 Cell Membrane NADPH Oxidases NOX4 Rats Endocrinology chemistry Dopamine receptor cardiovascular system biology.protein Reactive Oxygen Species medicine.drug |
| Zdroj: | Hypertension. 53:1054-1061 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.108.120642 |
| Popis: | NADPH oxidase (Nox)–dependent reactive oxygen species production is implicated in the pathogenesis of cardiovascular diseases, including hypertension. We tested the hypothesis that oxidase subunits are differentially regulated in renal proximal tubules from normotensive and spontaneously hypertensive rats. Basal Nox2 and Nox4, but not Rac1, in immortalized renal proximal tubule cells and brush border membranes were greater in hypertensive than in normotensive rats. However, more Rac1 was expressed in lipid rafts in cells from hypertensive rats than in cells from normotensive rats; the converse was observed with Nox4, whereas Nox2 expression was similar. The D 1 -like receptor agonist fenoldopam decreased Nox2 and Rac1 protein in lipid rafts to a greater extent in hypertensive than in normotensive rats. Basal oxidase activity was 3-fold higher in hypertensive than in normotensive rats but was inhibited to a greater extent by fenoldopam in normotensive (58±3.3%) than in hypertensive rats (31±5.2%; P phox in cells from normotensive rats. D 1 -like receptors may decrease oxidase activity by disrupting the distribution and assembly of oxidase subunits in cell membrane microdomains. The cholesterol-depleting reagent methyl–β-cyclodextrin decreased oxidase activity and cholesterol content to a greater extent in hypertensive than in normotensive rats. The greater basal levels of Nox2 and Nox4 in cell membranes and Nox2 and Rac1 in lipid rafts in hypertensive rats than in normotensive rats may explain the increased basal oxidase activity in hypertensive rats. |
| Databáze: | OpenAIRE |
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