Regulation of Cellular Activity by Reactive Oxygen

活性氧对细胞活性的调节

• 批准号: 08408028
• 负责人: TANIGUCHI Naoyuki
• 金额: $ 21.18万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08408028/
• 关键词: Reactive oxygen species; Antioxidants; Apoptosis; Diabetic complications; Glycation; Growth factor; 3-Deoxyglucosone; Signal transduction; 活性酸素; 一酸化窒素; 形質転換増殖因子; ヘパリン結合性上皮増殖因子; 2-オキソアルデヒド化合物; スーパーオキシドディスムターゼ; グルタチオンペルオキシダーゼ

We have investigated the glycation reaction which is assumed to be involved in aging and diabetes mellitus. Especially, effects of its early reaction products on antioxidative enzymes were examined. As results, cells exposed to reducing sugars such as fructose underwent apoptosis. On the other hand, 3-deoxyglucosone and methylglyoxal, reaction intermediates of the glycation reaction and very toxic compounds, were found to induce apoptosis in certain cells. An antibody was raised against fructated intermediary product of proteins with fructose (fructated lysine). We confirmed that crystallins were fructated in rat lens where the polyol metabolic pathway is active. In addition, we examined relationship between mechanism of induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) by glycation intermediates and growth of smooth muscle cells. Methylglyoxal and 3-deoxyglucosone induced HB-EGF expression in smooth muscle cells. While these intermediate increased the intracellular peroxides, N-acetylcysteine, an antioxidant, rather suppressed the gene expression. These data suggest that reactive oxygen species are somehow involved in the expression of HB-EGF gene.

我们已经研究了糖化反应，这被认为是参与衰老和糖尿病。特别是其早期反应产物对抗氧化酶的影响进行了研究。结果，暴露于还原糖如果糖的细胞发生凋亡。另一方面，3-脱氧葡糖醛酮和甲基乙二醛，糖化反应的反应中间体和非常有毒的化合物，被发现在某些细胞中诱导凋亡。针对蛋白质与果糖的果糖化中间产物（果糖化赖氨酸）产生抗体。我们证实，晶状体蛋白是果酸在大鼠透镜中的多元醇代谢途径是活跃的。此外，我们还研究了糖基化中间体诱导肝素结合表皮生长因子样生长因子（HB-EGF）的机制与平滑肌细胞生长之间的关系。甲基乙二醛和3-脱氧葡萄糖醛酸诱导平滑肌细胞表达HB-EGF。虽然这些中间体增加了细胞内的过氧化物，N-乙酰半胱氨酸，抗氧化剂，而抑制基因表达。这些数据表明，活性氧在某种程度上参与了HB-EGF基因的表达。

项目成果

M.Asahi: "The oxidation of selenocysteine is involved in the inactivation of glutathione peroxide by nitric oxide donor" J.Biol.Chem.272(in press). (1997)

M.Asahi：“硒代半胱氨酸的氧化参与一氧化氮供体对过氧化谷胱甘肽的失活”J.Biol.Chem.272（印刷中）。

H.Kaneto: "Expression of HB-EGF during pancreas development:a potential role of PDX-1 in the transcriptional activation." J.Biol.Chem.272. 29137-29143 (1997)

H.Kaneto：“胰腺发育过程中 HB-EGF 的表达：PDX-1 在转录激活中的潜在作用。”

W.Che: "Selective induction of heparin-binding epidermat growth factor-like growth dactor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells." J.Biol.Chem.272. 18453-18459 (1997)

W.Che：“甲基乙二醛和 3-脱氧葡萄糖酮在大鼠主动脉平滑肌细胞中选择性诱导肝素结合表皮生长因子样生长因子。”

M.Asahi: "The Oxidation of Selenocysteine is Involved in the Inactivation of Glutathione Peroxidase by Nitric Oxide Donor" J.Biol.Chem.272. 19152-19157 (1997)

M.Asahi：“硒代半胱氨酸的氧化参与一氧化氮供体对谷胱甘肽过氧化物酶的失活”J.Biol.Chem.272。

T.Nakagawa: "Amino-terminal processing of cell surface heparin-binding epidermal growth factor-like growth factor up-regulates its juxtacrine but not its paracrine growth factor activity" J.Biol.Chem.271. 30858-30863 (1996)

T.Nakakawa：“细胞表面肝素结合表皮生长因子样生长因子的氨基末端处理上调其近分泌，但不上调其旁分泌生长因子活性”J.Biol.Chem.271。