Role of oxidative DNA damage in the pathogenesis of diabetic complications

DNA氧化损伤在糖尿病并发症发病机制中的作用

• 批准号: 09671019
• 负责人: SUZUKI Susumu
• 金额: $ 1.92万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671019/
• 关键词: Oxidative stress; 8-oxo-2'-deoxyguanosine; mitochondrial DNA; diabetic nephropathy; diabetic retinopathy; アポトーシス; DNA損傷; 8-hydroxydeoxyguanosine

Augmented oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine(dG) to 8-oxo, 2'-deoxyguanosine (8-oxodG) in DNA.To investigate the possible. contribution of oxidative DNA damage to the pathogenesis of diabetic complicfttions, we measured the 8-oxodGcontents in the urine and the blood mononuclear cells of type 2 diabetic patients.The contents of 8-oxodG in the urine and the mononuclear cells of the type 2 diabetic patients were much higher than those of the control subjects. Urinary excretion of 8-oxodG was significantly correlated with the 8-oxodG content in the mononuclear cells (R=0.855, p<0.0001). The 8-oxodGcontents in the urine (R=0.783, p<0.0001) and mononuclear cells (R=0.796, p.<0.0001) were correlated with the hemoglobin A1c level. Urinary 8-oxodG excretion and the 8-oxodG content in the mononuclear cells were augmented in proportion to the severity of diabetic nephropathy as well as retinopathy. These data provide evidence that augmented oxidative DNA damage in diabetes is linked to diabetic complications.This is the first report showing that the increase in 8-oxodG is proportional to the severity of diabetic complications. Oxidative DNA damage is speculated to contribute to the pathogenesis of diabetic complications. 8-oxodG in urine and mononuclear cells is a useful marker to evaluate oxidative DNA damage in diabetic patients.

高血糖引起的氧化应激增强可能导致糖尿病并发症的发病机制。已知氧化应激会增加 DNA 中脱氧鸟苷 (dG) 向 8-氧代、2'-脱氧鸟苷 (8-oxodG) 的转化。为了研究这种可能性。为了探究氧化DNA损伤在糖尿病并发症发病机制中的贡献，我们测定了2型糖尿病患者尿液和血液单个核细胞中8-oxodG的含量。2型糖尿病患者尿液和血液单个核细胞中8-oxodG的含量均远高于对照组。 8-oxodG 的尿排泄量与单核细胞中 8-oxodG 含量显着相关（R=0.855，p<0.0001）。尿液中8-oxodG含量（R=0.783，p<0.0001）和单核细胞（R=0.796，p.<0.0001）与血红蛋白A1c水平相关。尿8-oxodG排泄量和单核细胞中8-oxodG含量随糖尿病肾病和视网膜病变的严重程度成比例增加。这些数据提供了证据，表明糖尿病中氧化 DNA 损伤的增强与糖尿病并发症有关。这是第一份表明 8-oxodG 的增加与糖尿病并发症的严重程度成正比的报告。据推测，DNA 氧化损伤是糖尿病并发症的发病机制之一。尿液和单核细胞中的 8-oxodG 是评估糖尿病患者氧化 DNA 损伤的有用标记。

项目成果

Yoshimori Hinokio: "Oxidative DNA domapes in Diabetes : Its association arth diabetic complications" Diabetologia. (1999)

Yoshimori Hinokio：“糖尿病中的氧化 DNA 多映射：其与糖尿病并发症的关联”Diabetologia。

Masashi Hirai: "Mitocondrial deoxyrionucleic acid3256 C-T mutation in an Japanese family with non-insulin dependent diabetes mellitus" J clin Endocrinol Metob. 83. 992-994 (1998)

Masashi Hirai：“患有非胰岛素依赖性糖尿病的日本家庭中的线粒体脱氧核糖核酸 3256 C-T 突变”J clin Endocrinol Metob。

Susumu Suzuki: "Effect of Non-insalin dependent diabetes on cyclosporin dizpostion" Biochem Pharm Ball. 20. 1026-1029 (1997)

Susumu Suzuki：“非胰岛素依赖型糖尿病对环孢菌素分布的影响”Biochem Pharm Ball。

M.Hirai, S.Suzuki, M.Onoda, Y.Hinokio, A.Hirai, M.Ohtomo, M.Chiba, S.Kasuga, Y.Satoh, H.Akai, S.Miyabayashi and T.Toyota.: "Mitochon-drial deoxyribonucleic acid 3256C-T mutation in an Japanese family with noninsulin dependent diabetes mellitus." J Clin En

M.Hirai、S.Suzuki、M.Onoda、Y.Hinokio、A.Hirai、M.Ohtomo、M.Chiba、S.Kasuga、Y.Satoh、H.Akai、S.Miyabayashi 和 T.Toyota。：

Yoshihiko Suzuki: "Diabetes associated with a novel 3264 mitochondrial tRNA Leu(uuR) mutation" Dicbetes Care. 20. 1134-1140 (1997)

Yoshihiko Suzuki：“与新型 3264 线粒体 tRNA Leu(uuR) 突变相关的糖尿病”Dicbetes Care。