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Diabetologia

, Volume 42, Issue 2, pp 222–232 | Cite as

Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-kB

  • M. A. Hofmann
  • S. Schiekofer
  • B. Isermann
  • M. Kanitz
  • M. Henkels
  • M. Joswig
  • A. Treusch
  • M. Morcos
  • T. Weiss
  • V. Borcea
  • A. K. M. Abdel Khalek
  • J. Amiral
  • H. Tritschler
  • E. Ritz
  • P. Wahl
  • R. Ziegler
  • A. Bierhaus
  • P. P. Nawroth
Short communication

Summary

Increased oxidative stress and subsequent activation of the transcription factor NF-kB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kB activation is evident in patients with diabetic nephropathy we used an Electrophoretic Mobility Shift Assay based semiquantitative detection system which enabled us to determine NF-kB activation in ex vivo isolated peripheral blood mononuclear cells. We examined 33 patients with diabetes mellitus (Type I and Type II). Patients with diabetic nephropathy showed higher NF-kB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kBp65 than patients without renal complications. NF-kB binding activity correlated with the degree of albuminuria (r = 0.316) and with thrombomodulin plasma concentrations (r = 0.33), indicative for albuminuria associated endothelial dysfunction. In a 3 day intervention study in which 600 mg of the antioxidant thioctic acid (α-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48 % and NF-kB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38 %.

Keywords Oxidative stress nephropathy transcription factor NF-kB thrombomodulin thioctic acid. 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • M. A. Hofmann
    • 1
  • S. Schiekofer
    • 1
  • B. Isermann
    • 1
  • M. Kanitz
    • 1
  • M. Henkels
    • 1
  • M. Joswig
    • 1
  • A. Treusch
    • 1
  • M. Morcos
    • 1
  • T. Weiss
    • 1
  • V. Borcea
    • 1
  • A. K. M. Abdel Khalek
    • 1
  • J. Amiral
    • 2
  • H. Tritschler
    • 3
  • E. Ritz
    • 1
  • P. Wahl
    • 1
  • R. Ziegler
    • 1
  • A. Bierhaus
    • 1
  • P. P. Nawroth
    • 1
  1. 1.Department of Medicine, University of Heidelberg, Heidelberg, GermanyDE
  2. 2.Serbio Gennevilliers, FranceFR
  3. 3.ASTA Medica, Frankfurt am Main, GermanyDE

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