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Nuclear translocation of antioxidant enzymes and ROS metabolism

抗氧化酶的核转位和ROS代谢

基本信息

批准号：
18590305
负责人：
SUZUKI Keiichiro
金额：
$ 2.49万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590305/
关键词：
reactive oxygen species sugar chain LEC rat cleavage of oligosaccharides Cu, Zn-SOD 糖鎖 Cu Zn-SOD グリコサミノグリカン活性酸素トランスフェリン銅イオンヒアルロン酸プロテオグリカン SOD

项目摘要

Reactive oxygen species (ROS) are produced during several pathological conditions such as in inflammation and reperfusion injury and damage various biologicalmolecules due to its high and non-specific reactivity. We previously demonstrated that the glycosidic linkages of G1cNAc residues ofN-linked oligosaccharides are degraded by treatment with ROS generated by copper ions and hydrogen peroxides. We also found that the treatment of endothelial cells with ROS accelerates adhesion of neutrophils or colon cancer cells without any de novo synthesis of adhesion molecules, such as P-selectin, E-selectin, and ICAM-1, suggesting that ROS modify the endothelium glycocalyx, a network of charge-bearing glycoproteins and glycosaminoglycans that cover the luminal surface of endothelium cells, and cause this enhancement of adhesion. The Long Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, spontaneously develops hepatitis as the result of abnormal copper accumulation in liver. The -ndi … More ngs of this study show that copper, hydrogen peroxide, and lipid peroxides accumulite to drastically high levels in LEC rat serum in acute hepatitis but not chronic hepatitis. The e-ect of these reactive oxygen species (ROS) on oligosaccharides of glycoproteins in the LEC rat serum was examined. Lectin blot and lectin ELISA analyses showed that sialic acid and galactose residues of serum glycoproteins including transferrin were decreased in acute hepatitis. Further analyses of oligosaccharide structures of transferrin demonstrated that di-sialylated and asialo-agalacto biantennary sugar chains, but not tri-sialylated sugar chain, exist on transferrin in the acute hepatitis rats. In addition, treatment of non-hepatitis rat serum with copper ions and hydrogen peroxide decreased tri-sialylated sugar chain of the normal transferrin and increased di-sialylated and asialo-agalacto biantennary sugar chains. This is the first evidence to show that ROS result in the cleavage of oligosaccharides of glycoproteins in vivo, and indicate this cleavage of oligosaccharides may contribute the development of acute hepatitis. Less

活性氧(ROS)是在炎症和再灌注损伤等多种病理条件下产生的，具有高度的非特异性反应性，可损伤多种生物分子。我们以前曾证明，在铜离子和过氧化氢产生的ROS处理下，N-连接的寡糖的G1cNAc残基的糖苷键被降解。我们还发现，用ROS处理内皮细胞可以加速中性粒细胞或结肠癌细胞的黏附，而不会重新合成黏附分子，如P-选择素、E-选择素和ICAM-1，这表明ROS改变了内皮糖萼，内皮细胞管腔表面覆盖的荷电糖蛋白和糖胺多糖的网络，并导致这种黏附的增强。长埃文斯肉桂(Long Evans Cinnamon，LEC)大鼠是威尔逊病的动物模型，由于肝脏中铜的异常积聚，大鼠会自发发展为肝炎。-ndi…这项研究的更多NGS表明，在急性肝炎而不是慢性肝炎中，铜、过氧化氢和过氧化脂质在LEC大鼠血清中积累到极高的水平。本文研究了这些活性氧(ROS)对LEC大鼠血清糖蛋白寡糖的影响。凝集素印迹和凝集素ELISA法分析表明，急性肝炎患者血清糖蛋白包括转铁蛋白的唾液酸和半乳糖残基减少。进一步分析转铁蛋白的寡糖结构表明，急性肝炎大鼠转铁蛋白上存在二唾液酸化糖链和去唾液酸去乙酰半乳糖链，而不存在三唾液酸化糖链。此外，非肝炎大鼠血清经铜离子和过氧化氢处理后，正常转铁蛋白的三唾液酸化糖链减少，二唾液酸化糖链和去唾液酸化去唾液酸双天线糖链增加。这是首次有证据表明ROS导致体内糖蛋白寡糖的裂解，提示这种寡糖的裂解可能在急性肝炎的发生发展中起作用。较少