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

Diabetologia. 1999 Feb;42(2):222-32. doi: 10.1007/s001250051142.


Increased oxidative stress and subsequent activation of the transcription factor NF-kappaB has been linked to the development of late diabetic complications. To determine whether oxidative stress dependent NF-kappaB 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-kappaB 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-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications. NF-kappaB 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 (alpha-lipoic acid) per day were given to nine patients with diabetic nephropathy oxidative stress in plasma samples was decreased by 48% and NF-kappaB binding activity in ex vivo isolated peripheral blood mononuclear cells by 38%. In conclusion, activation of the transcription factor NF-kappaB in ex vivo isolated peripheral blood mononuclear cells of patients with diabetes mellitus correlates with the degree of diabetic nephropathy. NF-kappaB activation is at least in part dependent on oxidative stress since thioctic acid (alpha-lipoic acid) reduced NF-kappaB binding activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria
  • Antioxidants / therapeutic use
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetic Nephropathies / blood*
  • Female
  • Humans
  • Leukocytes, Mononuclear / physiology*
  • Male
  • Middle Aged
  • NF-kappa B / blood*
  • Oxidative Stress*
  • Thioctic Acid / therapeutic use
  • Thrombomodulin / blood


  • Antioxidants
  • NF-kappa B
  • Thrombomodulin
  • Thioctic Acid