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.

有一些证据表明氧化DNA损伤与糖尿病并发症可能存在关系。我们证明了正常人和2型糖尿病患者尿和/或白细胞8-oxodG与胰岛素敏感性之间的显着关系。我们还在一项横断面研究中证明了尿和/或白细胞8-oxodG与糖尿病肾病和视网膜病变的严重程度之间的显著关系。我们在一项前瞻性研究中证实了尿8-oxodG水平与肾病发展之间的显著相关性。这项前瞻性研究还证明了白细胞8-oxodG水平与视网膜病变的发展之间的显著相关性。因此，本研究为氧化应激增加在糖尿病肾病和视网膜病变的发病机制中起主要作用提供了证据。我们还开发了一种新的检测系统，利用气相色谱/质谱（GC/MS）检测嘧啶氧化产物、嘌呤氧化产物、碱脱氨产物、碱氯化产物。使用该检测系统，我们已经进行了糖尿病和糖尿病并发症的发病机制中的氧化DNA损伤的精确表征。

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。

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)

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。