The activation of NF-κB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy

Ji Sun Nam, Min Ho Cho, Geun Taek Lee, Jong Suk Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee

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Abstract

We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC) in 66 diabetic patients with or without diabetic nephropathy (Groups III and II, respectively) and 49 normal controls (Group I). Stimulated ROS was significantly higher in Group III compared to Group II (increment of H2O2-induced ROS production: 21.8 ± 2.2% vs. 11.1 ± 2.0%; increment of PMA-induced ROS production 23.5 ± 4.5% vs. 21.6 ± 2.2%; both respectively), and the activity of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), but not specificity protein 1 (Sp1) was significantly higher in Group III than in Group II (2.53-fold vs. 2.0-fold vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-β1 levels were higher in Group III than Group II (3.23 ± 0.39 ng/g vs. 1.99 ± 0.68 ng/g in PBMCs, 16.88 ± 6.84 (ng/g Cr) vs. 5.61 ± 1.57 (ng/g Cr) in urine, both respectively), and they correlated with the activity of NF-κB and AP-1 and 24-h urine albumin excretion (UAE). Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy via activation NF-κB and AP-1 and an increased expression of TGF-β1.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalDiabetes Research and Clinical Practice
Volume81
Issue number1
DOIs
Publication statusPublished - 2008 Jul 1

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All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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