Rosiglitazone Reduces Angiotensin II and Advanced Glycation End Product-dependent Sustained Nuclear Factor-κB Activation in Cultured Human Proximal Tubular Epithelial Cells

M. Morcos; A. Schlotterer; A. A. R. Sayed; G. Kukudov; D. Oikomonou; Y. Ibrahim; F. Pfisterer; J. Schneider; F. Bozorgmehr; G. Rudofsky Jr.; V. Schwenger; R. Kientsch-Engels; A. Hamann; M. Zeier; K. Dugi; B. Yard; P. M. Humpert; F. van der Woude; P. P. Nawroth; A. Bierhaus

doi:10.1055/s-0028-1082039

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2008; 40(11): 752-759
DOI: 10.1055/s-0028-1082039

Original Basic

Rosiglitazone Reduces Angiotensin II and Advanced Glycation End Product-dependent Sustained Nuclear Factor-κB Activation in Cultured Human Proximal Tubular Epithelial Cells

M. Morcos¹ , A. Schlotterer¹ , A. A. R. Sayed¹ , G. Kukudov¹ , D. Oikomonou¹ , Y. Ibrahim¹ , F. Pfisterer¹ , J. Schneider¹ ^, ² , F. Bozorgmehr¹ , G. Rudofsky Jr.¹ , V. Schwenger¹ , R. Kientsch-Engels³ , A. Hamann¹ ^, ⁶ , M. Zeier¹ , K. Dugi⁴ , B. Yard⁵ , P. M. Humpert¹ , F. van der Woude⁵ , P. P. Nawroth¹ , A. Bierhaus¹

¹Department of Internal Medicine 1 (Endocrinology, Metabolism and Clinical Chemistry) & Renal Department, University of Heidelberg, Germany
²Teaching Hospital Merzig/Saar, University of Saarland, Germany
³Roche Diagnostics, Penzberg, Germany
⁴Boehringer Ingelheim Corporation, Ingelheim, Germany
⁵V Medical Clinic, University of Mannheim, Germany
⁶Diabetes Clinic Bad Nauheim, Germany

Abstract

Tubular damage is a major feature in the development of diabetic nephropathy. This study investigates the effects of the thiazolidindione rosiglitazone on angiotensin II and advanced glycation end product-induced tubular activation in human proximal tubular epithelial cells in vitro. Angiotensin II and advanced glycation end products, both induced a dose-dependent sustained activation of the redox-sensitive transcription factor, Nuclear Factor kappa B (NF-κB). Nuclear translocation of NF-κB was evident already after one hour and persistent for more than four days. Co-incubation of proximal tubular epithelial cells with rosiglitazone significantly reduced angiotensin II and advanced glycation end product-mediated generation of reactive oxygen species, angiotensin II-dependent advanced glycation end product formation, NF-κB activation, and NF-κB-dependent pro inflammatory gene expression. Most importantly, rosiglitazone effects on NFκB activation were maximal at later time points, indicating that rosiglitazone treatment confers long lasting renoprotective effects.

Key words

cellular activation - late diabetic complication - diabetic nephropathy - thiazolidindiones - reactive oxygen species

Full Text

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Correspondence

Dr. M. Morcos

Department of Internal Medicine 1 (Endocrinology, Metabolism and Clinical Chemistry) & Renal Department

University of Heidelberg

INF 410

69120 Heidelberg

Germany

Phone: +49/6221/56 86 14

Fax: +49/6221/56 68 48

Email: michael_morcos@med.uni-heidelberg.de