Development of a new assay method for oxidative DNA damages in diabetes

开发糖尿病 DNA 氧化损伤的新检测方法

• 批准号: 12671096
• 负责人: SUZUKI Susumu
• 金额: $ 2.18万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671096/
• 关键词: Diabetes mellitus; Diabetic complication; Diabetic nephropathy; Diabetic retinopathy; Oxidative stress; Oxidative DNA damage; GC-MS; 8-oxo-deoxyguanosine; 8-OXO-deoxyguanosine; DNA損傷; 活性酸素

There were several line of evidence to demonstrate a possible relationship oxidative DNA damages and diabetic complications. We demonstrated a significant relationship between the urinary and/or leukocyte 8-oxodG and insulin sensitivity in normal subjects and type 2 diabetic patients. We also demonstrated significant relationship between the urinary and/or leukocyte 8-oxodG and the severity of diabetic nephropathy and retinopathy in a cross-sectional study. We demonstrates a significant association between the urinary 8-oxodG levels and the development of nephropathy in a prospective study. This prospective study also demonstrates a significant association between the leukocyte 8-oxodG levels and the development of retinopathy. Thus, the study provides evidence that augmented oxidative stress has a primary role in the pathogenesis of diabetic nephropathy and retinopathy.We also developed the new assay system using gas-chromatography/mass spectrometry (GC/MS) to measure pyrimidine oxidation products, purine oxidation products, base deamination products, base chlorination products. Using this assay system, we have performed the precise characterization of oxidative DNA damages in diabetes mellitus and pathogenesis of diabetic complications.

有几种证据证明可能存在关系的氧化DNA损害和糖尿病并发症。我们证明了正常受试者和2型糖尿病患者的尿和/或白细胞8-oxoDG和胰岛素敏感性之间存在显着关系。在一项横断面研究中，我们还展示了尿和/或白细胞8-OXODG与糖尿病性肾病和视网膜病的严重程度之间的显着关系。我们在一项前瞻性研究中证明了尿8-氧气水平与肾病的发展之间存在显着关联。这项前瞻性研究还表明，白细胞8-OXODG水平与视网膜病的发展之间存在显着关联。因此，该研究提供了证据，表明增强的氧化应激在糖尿病性肾病和视网膜病的发病机理中具有主要作用。我们还使用气体色谱/质谱/质谱仪（GC/MS）开发了新的测定系统，以测量嘧啶氧化产物，嘌呤氧化产物，碱基氧化产物，脱氨基水平产物，碱基氯化产物，碱基氯化产物。使用此测定系统，我们对糖尿病中氧化DNA损伤的精确表征以及糖尿病并发症的发病机理。

项目成果

A.Abderrahmani: "Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in Frech Caucasians"Diabetes. 49. 306-308 (2000)

A.Abderrahmani：“肝细胞核因子 3β 基因 (HNF3B) 的遗传变异不会导致法国白种人年轻人的成年期糖尿病”。

Koga Komatsu: "Cre-Loxp-mediated bax gene activation"Cancer Gene Ther. 7. 885-892 (2000)

Koga Komatsu：“Cre-Loxp 介导的 bax 基因激活”癌症基因疗法。

K.komatsu: "Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells"Cancer Gene Ther. 7. 885-892 (2000)

K.komatsu：“Cre-loxP 介导的 bax 基因激活可降低人胃癌细胞的生长速度并增加对化疗药物的敏感性”Cancer Gene Ther。

F.Okamura: "Insulin resistance in patients with depression and its changes during the clinical course of depression : minimal model analysis"Metabolism. 49. 1255-1260 (2000)

F.Okamura：“抑郁症患者的胰岛素抵抗及其在抑郁症临床过程中的变化：最小模型分析”代谢。

Komafsu K.: "Cre-loxP-mediated bax gene activation reduces growth rate and increasest sensitivity to chemotherapy."Cancer Gene Ther.. 7. 885-892 (2000)

Komafsu K.：“Cre-loxP 介导的 bax 基因激活可降低生长速度并增加对化疗的敏感性。”Cancer Gene Ther.. 7. 885-892 (2000)