2007 Fiscal Year Final Research Report Summary
Nuclear translocation of antioxidant enzymes and ROS metabolism
| Project/Area Number |
18590305
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
SUZUKI Keiichiro Hyogo College of Medicine, Faculty of Medicine, Professor (70221322)
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| Co-Investigator(Kenkyū-buntansha) |
OOKAWARA Tomomi Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (50330452)
FUJIWARA Noriko Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (10368532)
YOKOE Syunichi Hyogo College of Medicine, Faculty of Medicine, Instructor (40454756)
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| Project Period (FY) |
2006 – 2007
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| Keywords | reactive oxygen species / sugar chain / LEC rat / cleavage of oligosaccharides / Cu, Zn-SOD |
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| Research Abstract |
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
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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
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Research Products
(14 results)
