KMID : 0354720070310030261
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Journal of Korean Diabetes Association 2007 Volume.31 No. 3 p.261 ~ p.273
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Activation of NF-¥êB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy
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Nam Ji-Sun
Cho Min-Ho Park Jong-Suk Lee Geun-Taek Kim Hai-Jin Kang Eun-Seok Rhee Yu-Mie Ahn Chul-Woo Cha Bong-Soo Lee Eun-Jig Lim Sung-Kil Kim Kyung-Rae Ha Hun-joo Lee Hyun-Chul
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Abstract
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Background: 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).
Methods: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and
49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-¥êB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-¥â1 (transforming growth factor-¥â1), and 24-hour urinary albumin excretion (UAE) were measured.
Results: Spontaneous ROS was significantly higher in group III and II than group I (60.7 ¡¾ 3.3 vs. 60.0 ¡¾ 3.0 vs. 41.1 ¡¾ 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 ¡¾ 2.2 vs. 11.1 ¡¾ 2.0%, respectively; increment of PMA-induced ROS production 23.5 ¡¾ 4.5 vs. 21.6 ¡¾ 2.2%, respectively). The activities of NF-¥êB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-¥â1 levels were higher in Group III than Group II (3.23 ¡¾ 0.39 vs. 1.99 ¡¾ 0.68 ng/mg in PBMCs, 16.88 ¡¾ 6.84 vs. 5.61 ¡¾ 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-¥êB and AP-1 and 24-hour UAE.
Conclusions: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the athogenesis of diabetic nephropathy through activation of NF-¥êB and AP-1, but not Sp1, and increased expression of TGF-¥â1
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KEYWORD
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AP-1, Diabetic nephropathy, NF-¥êB, Oxidative stress, Sp1, TGF-¥â1
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