Reactive oxygen species modify oligosaccharides of glycoproteins in vivo: a study of a spontaneous acute hepatitis model rat (LEC rat).
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 findings of this study show that copper, hydrogen peroxide, and lipid peroxides accumulate to drastically high levels in LEC rat serum in acute hepatitis but not chronic hepatitis. The effect 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.
Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Jun
J
Yasuda
Hironobu
H
Eguchi
Noriko
N
Fujiwara
Tomomi
T
Ookawara
Shoudou
S
Kojima
Yukihiro
Y
Yamaguchi
Masashi
M
Nishimura
Jiro
J
Fujimoto
Keiichiro
K
Suzuki
D000208:Acute Disease; D000818:Animals; D002236:Carbohydrate Conformation; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D006520:Hepatitis, Animal / Q000151:congenital / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D020332:Rats, Inbred LEC; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
D006023:Glycoproteins; D009844:Oligosaccharides; D017382:Reactive Oxygen Species; D014168:Transferrin