Basic research in the connection of the cause of development of symptoms of diabetes and its complication

糖尿病症状发生原因及其并发症关系的基础研究

• 批准号: 10470531
• 负责人: YAMAGUCHI Tadatoshi
• 金额: $ 3.26万
• 依托单位: Miyazaki Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470531/
• 关键词: dihydropyrazine; DNA strand breakage; dihydrodiazepine; carbon-centered radical diabetes; diabetes; cultured cell; apoptosis; carbon-centeral radical; dihydropyrazime; DNA strand-breaKage; carbom-centered radical; Diabetes; DNA Strand-breakage

Elucidation of the mechanism of DNA strand-breakage by D-glucosamine, was attempted to clear. Then we aimed at applying the enlightened results for diabetic prevention and medical treatment. It is hitherto cleared that dihydrofructosazine which was derived from D-glucosamine, has a DNA strand-breakage activity. Thus, dihydropyrazines (DHPs), similar structure to dihydrofructosazine, were synthesized and recognized to reveal the activity. Some remarkable properties of DHPs have been revealed as shown in bellows.1. DNA strand-breakage activity2. Generation of hydroxyl and carbon-centered radicals3. Noble chemical reaction4. Nucleotide sequence specificity in DNA cleavageFurther, certain new facts are beginning to become apparent. That is to say, the autoradiogram of ^<14>C-labeled DHP showed that high uptake of ^<14>C-labeled DHP was observed in the spinal cord and also the brain. The effects of DHPs on cellular viability by culture assay of several cell lines, were examined. Cell morphological changes and the induction of apoptosis-related proteins were detected.If the presence and the production of DHPs in vitro were exhibited, the connection of DHPs with certain diseases will be elucidated in future.

试图阐明D-氨基葡萄糖引起DNA链断裂的机制。并将研究成果应用于糖尿病的预防和治疗。到目前为止，从D-氨基葡萄糖衍生出来的二氢果糖嗪具有DNA断链活性。因此，合成了结构类似于二氢果糖嗪的二氢吡嗪类化合物(DHPs)，并对其进行了识别，以揭示其活性。DHPS的一些显著性质已被揭示如下1。DNA链断裂活性。生成羟基和碳心自由基3。高尚的化学反应。DNA切割中的核苷酸序列特异性此外，某些新的事实开始变得明显。也就是说，~(14)C标记DHP的放射自显影显示，~(14)C标记的DHP在脊髓和脑中都有较高的摄取。通过几种细胞系的培养实验，检测了DHPS对细胞活力的影响。检测了细胞的形态变化和诱导凋亡相关蛋白的表达。如果在体外显示DHPs的存在和产生，则DHPs与某些疾病的联系将在未来得到阐明。

项目成果

T.Yamaguchi et al.: "A Carbon-centered Radical as a Reaction Species in the DNA strand-Breakage by D-Glucoeamine"Biol. Pharm. Bull.. 21. 205-209 (1998)

T.Yamaguchi 等人：“DNA 链中以碳为中心的自由基作为反应种类 - D-葡萄糖胺造成的断裂”Biol。

Nobuhiro Kashige, Tadatoshi Yamaguchi, Fumio Miake, and Kenji Watanabe: "Nucleotide Sequence Specificity in DNA Cleavage Caused by Dihydropyrazines, a New Type of DNA Strand-Cleaving Agent,"Biol. Pharm. Bull.. 23. 1281-1286 (2000)

Nobuhiro Kashige、Tadatoshi Yamaguchi、Fumio Miake 和 Kenji Watanabe：“二氢吡嗪（一种新型 DNA 链切割剂）引起的 DNA 切割中的核苷酸序列特异性”Biol。

N.Kashige et al.: "Nucleotide Sequence Specificity in DNA Cleavage caused by Dihydropyrazines, a New Type of DNA Strand-cleaving Agent"Biol. Pharm. Bull.. 23. 1281-1286 (2000)

N.Kashige 等人：“二氢吡嗪（一种新型 DNA 链切割剂）引起的 DNA 切割中的核苷酸序列特异性”Biol。

Hiraku, Y., Sugimoto, J., Yamaguchi, T. and Kawanishi, S.: "Oxidative DNA Damage Induced by Aminoacetone, an Amino Acid Metabolite"Archives of Biochemistry and Biophysics. 365. 62-70 (1999)

Hiraku, Y.、Sugimoto, J.、Yamaguchi, T. 和 Kawanishi, S.：“氨基酸代谢物氨基丙酮诱导的氧化 DNA 损伤”生物化学和生物物理学档案。

Yamaguchi, T., Kashige, N., Matsumoto, S., Satoh, K., Yasuda, M. and Watanabe, K.: "A Carbon-Centered Radical as a Reaction Species in the DNA Strand-Breakage by D-Glucosamine"Biol. Pharm. Bull.. 21. 205-209 (1998)

Yamaguchi, T.、Kashige, N.、Matsumoto, S.、Satoh, K.、Yasuda, M. 和 Watanabe, K.：“以碳为中心的自由基作为 D-葡萄糖胺 DNA 链断裂中的反应物种