Thiazolidinediones inhibit albumin uptake by proximal tubular cells through a mechanism independent of peroxisome proliferator activated receptor gamma

American Journal of Nephrology
Ravinder S Chana, Nigel J Brunskill

Abstract

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. We investigated the potentially beneficial effects of TZDs in opossum kidney proximal tubular cells, focussing particularly on protein handling. 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. TZDs inhibit albumin uptake and cholesterol synthesis in proximal tubular cells...Continue Reading

References

Nov 3, 1994·The New England Journal of Medicine·J J NolanJ Olefsky
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·S A KliewerR M Evans
Jul 11, 1996·Nature·C LamazeS L Schmid
Nov 24, 1999·The American Journal of Physiology·T YangA K Mircheff
Jan 12, 2000·Current Opinion in Nephrology and Hypertension·G Remuzzi
Apr 13, 2000·Biochimica Et Biophysica Acta·M Sinensky
Jun 6, 2000·Nature·S KerstenW Wahli
Dec 15, 2000·Kidney International·K J McCarthyJ H Johnson
Dec 31, 2002·Journal of the American Society of Nephrology : JASN·Mustafa AriciNigel John Brunskill
Jun 6, 2003·Kidney International·Siddhartha S GhoshAnton C Schoolwerth
Jan 30, 2004·Journal of the American Society of Nephrology : JASN·Nigel J Brunskill
May 29, 2004·Trends in Pharmacological Sciences·Shamina M Rangwala, Mitchell A Lazar
Sep 2, 2004·Journal of the American Society of Nephrology : JASN·James E SidawayNigel J Brunskill
Feb 4, 2005·Journal of the American Society of Nephrology : JASN·Stephen ZafiriouCarol A Pollock
Feb 16, 2005·Annual Review of Physiology·Michael Gekle

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Citations

May 20, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ernie HarpurUNKNOWN HESI Committee on Biomarkers of Nephrotoxicity
Sep 29, 2012·Pharmacology & Therapeutics·Hong-Guang XieErnie Harpur
Jan 1, 2008·PPAR Research·Eva Kiss-Tóth, Tamás Roszer
Jun 15, 2007·Current Opinion in Nephrology and Hypertension·Carol A Pollock, Philip Poronnik

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