title: The activation of NF-kappaB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy.
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 H(2)O(2)-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-kappaB) 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-beta1 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-kappaB 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-kappaB and AP-1 and an increased expression of TGF-beta1.
authors.affiliation: Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Nam
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Cho
authors.forename: Geun Taek
authors.initials: GT
authors.lastname: Lee
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Park
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
authors.forename: Sung Kil
authors.initials: SK
authors.lastname: Lim
authors.forename: Kyung Rae
authors.initials: KR
authors.lastname: Kim
authors.forename: Hun Joo
authors.initials: HJ
authors.lastname: Ha
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000097:blood*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000097:blood*
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1