| Thiazolidinediones inhibit albumin uptake by proximal tubular cells through a mechanism independent of peroxisome proliferator activated receptor gamma. | |
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MedLine Citation:
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PMID: 16508249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor which exerts multiple effects on target cell function. A variety of PPARgamma ligands are known, including the antidiabetic thiazolidinediones (TZDs). There is evidence that suggests that these drugs may improve metabolic parameters, proteinuria, and blood pressure in type 2 diabetes. METHOD: We investigated the potentially beneficial effects of TZDs in opossum kidney proximal tubular cells, focussing particularly on protein handling. RESULTS: Three TZDs, ciglitazone, rosiglitazone, and troglitazone, all inhibited FITC-albumin uptake by cells in a dose-dependent manner in the absence of cell cytotoxicity or effects on binding. In contrast, the structurally unrelated PPARgamma ligand 15d-PGJ2 had no effect on albumin uptake. In cells overexpressing PPARgamma or treated with the PPARgamma antagonist GW9662, no alterations in the inhibitory effects of TZDs were observed. All TZDs reduced cholesterol synthesis, and supplementation of cells with non-sterol precursors of cholesterol, mevalonate, farnesol, and geranylgeranyl pyrophosphate, reversed the effects of TZDs. CONCLUSIONS: TZDs inhibit albumin uptake and cholesterol synthesis in proximal tubular cells independently of PPARgamma. Depletion of cholesterol precursors by TZDs is at least partially responsible for reduced albumin uptake. These results support a new role for TZDs to combat progressive proteinuric renal disease. |
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Authors:
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Ravinder S Chana; Nigel J Brunskill |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-02-28 |
Journal Detail:
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Title: American journal of nephrology Volume: 26 ISSN: 0250-8095 ISO Abbreviation: Am. J. Nephrol. Publication Date: 2006 |
Date Detail:
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Created Date: 2006-04-07 Completed Date: 2006-08-11 Revised Date: 2007-02-14 |
Medline Journal Info:
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Nlm Unique ID: 8109361 Medline TA: Am J Nephrol Country: Switzerland |
Other Details:
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Languages: eng Pagination: 67-74 Citation Subset: IM |
Copyright Information:
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Copyright 2006 S. Karger AG, Basel |
Affiliation:
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Department of Infection, Immunity and Inflammation, Faculty of Medicine and Biological Sciences, University of Leicester, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Albumins
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metabolism Anilides / pharmacology Animals Cells, Cultured Cholesterol / biosynthesis Chromans / pharmacology Farnesol / pharmacology Kidney Tubules, Proximal / drug effects* Ligands Mevalonic Acid / pharmacology Opossums PPAR gamma / antagonists & inhibitors, physiology* Polyisoprenyl Phosphates / pharmacology Thiazoles / pharmacology* Thiazolidinediones / pharmacology Thiazolidines |
| Chemical | |
Reg. No./Substance:
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0/2-chloro-5-nitrobenzanilide; 0/Albumins; 0/Anilides; 0/Chromans; 0/Ligands; 0/PPAR gamma; 0/Polyisoprenyl Phosphates; 0/Thiazoles; 0/Thiazolidinediones; 0/Thiazolidines; 122320-73-4/rosiglitazone; 150-97-0/Mevalonic Acid; 4602-84-0/Farnesol; 5685-05-2/thiazoline-2-thione; 57-88-5/Cholesterol; 6699-20-3/geranylgeranyl pyrophosphate; 74772-77-3/ciglitazone; 97322-87-7/troglitazone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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