- Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.
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Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee
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Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.3.261
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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-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), 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 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB 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-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.
- Protective Effects of Lithospermate B on Diabetic Nephropathy in OLETF Rat.
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Hyun Joo Lee, Geun Taek Lee, Eun Seok Kang, Kyu Yeon Hur, Zheng Shan Zhao, Chul Woo Ahn, Hun Joo Ha, Man Kil Jung, Bong Soo Cha, Hyun Chul Lee
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Korean Diabetes J. 2005;29(4):322-332. Published online July 1, 2005
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Abstract
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Magnesium lithospermate B(LAB), an active component isolated from Salvia milltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal model. The purpose of this study was to examine the effects of LAB on the prevention of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty(OLETF) rat which is regarded as an animal model of type 2 diabetes. METHODS: Ten microgram of LAB/kg or Vehicle(PBS) was given orally once daily to 10-week-old male OLETF rats and LETO rats for 40 weeks. Intra-peritoneal glucose tolerance test was performed at 50 weeks. 24 hr urinary protein excretion amounts were measured. Lipid peroxidation, TGF-beta1 and ED-1 of renal cortex were measured. RESULTS: The mean body weight of LAB+OLETF was not significantly different from that of OLETF rats. LAB treatment decreased proteinuria, lipid peroxidation, and free fatty acid in OLETF rats without decrease in the plasma glucose concentration. Also, LAB inhibited the progression of glomerular hypertrophy and mesangial expansion. LAB effectively decreased ED-1 positive cells, ECM expansion, and TGF-beta1 level in the renal cortex of OLETF rats. CONCLUSIONS: These results suggest that the beneficial effects of LAB on the diabetic renal damage in the OLETF rats may depend on a mechanism of decreasing oxidative stress. LAB might be a new therapeutic agent for the prevention of nephropathy in type 2 diabetes as well as type 1 diabetes.
- Role of Activation of NF- B and AP-1 by Oxidative Stress in Atherosclerosis in Diabetic Patients.
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Chul Sik Kim, Geun Taek Lee, Jina Park, Min Ho Cho, Joo Young Nam, Jong Suk Park, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee
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Korean Diabetes J. 2004;28(4):255-264. Published online August 1, 2004
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The aim of this study was to evaluate the possible role of NF- B activation and AP-1 by oxidative stress in atherosclerosis in diabetic patients by measuring the carotid intima-media thickness, intracellular ROS generation and activation of transcription factors, including nuclear factor-kappa B (NF- B) and activator protein-1 (AP-1). METHODS: Sixty-six patients (28 males, 38 females; age 56.1 13.4 years; duration of diabetes 115.7 83.4 months) with type 2 diabetes mellitus (DM) were selected for this study. The DM patients included in this study were divided into those with a normal carotid intima-media thickness (Group II) and those with an increased intima-media thickness (Group III). 57 healthy controls matched for age and sex with the DM patients (Group I) were randomly selected. Dichlorodifluorescein (DCF)-sensitive intracellular ROS was measured by fluorescent spectrometry. The activities of NF- B and AP-1 in PBMCs were measured by an electrophoretic mobility shift assay. RESULTS: No differences were evident between the groups in terms of gender, age, BMI, blood pressure, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. Spontaneous and H2O2 (or phorbol-12-myristate-13-acetate, PMA) stimulated ROS were significantly higher in the PBMCs from the DM patients with an increased intima-media thickness (Group III) than in those without (Group II), and were also higher in the control group (Group I). Moreover, the activities of NF- B and AP-1 were significantly higher in Group III than in Groups I or II. CONCLUSION: The present study demonstrates that intracellular ROS generation, and NF- B and AP-1 activation in PBMCs strongly correlates with the carotid artery IMT. These clinical results suggest that increased oxidative stress in PBMCs may play a role in the pathogenesis of atherosclerosis in DM patients .
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