The activation of NF-kappaB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy.
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.
Nam
Ji Sun
JS
Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea.
Cho
Min Ho
MH
Lee
Geun Taek
GT
Park
Jong Suk
JS
Ahn
Chul Woo
CW
Cha
Bong Soo
BS
Lim
Sung Kil
SK
Kim
Kyung Rae
KR
Ha
Hun Joo
HJ
Lee
Hyun Chul
HC
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*
D002784:Cholesterol; D006442:Glycated Hemoglobin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1