title: A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylnitrosamine (DEN): identification of haptoglobin as a target molecule of GnT-III.
abstract: A glycomic approach to the identification of target molecules in glycosyltransferase gene targeting mice is a promising strategy to understand the biological significance of glycosyltransferase genes in vivo. In order to understand the biological effects of N-acetylglucosaminyltransferase III (GnT-III) on tumor formation in the liver, diethylnitrosamine (DEN) induced tumor formation in the GnT-III transgenic mice was examined. Our findings show that the incidence of hepatic tumor could be dramatically suppressed. A glycomic approach using two-dimensional gel electrophoresis followed by lectin blot analysis and sequence analysis revealed that haptoglobin, a radical scavenger molecule in serum was heavily glycosylated in hepatic tumor-bearing GnT-III transgenic mice that had been treated with DEN. Immunoprecipitation followed by E4-PHA lectin blot analysis also confirmed that the bisecting GlcNAc, a product of GnT-III was added to haptoglobin molecules. Since the use of DEN is known to lead to the production of lipid peroxidation products which facilitate this reaction and haptoglobin is an acute phase reactant, acting as a radical scavenger against hemoglobin or iron stimulated lipid peroxidation, a relationship between the glycosylation of haptoglobin and the suppression of hepatoma development can not be ruled out. This paper is the first report that shows a relationship between the sugar chains of glycoproteins with radical scavenger activity and hepatocarcinogenesis.
authors.affiliation: Department of Biochemistry, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ekuni
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Ko
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Noda
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kitada
authors.forename: Shinji
authors.initials: S
authors.lastname: Ihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Endo
authors.forename: Asako
authors.initials: A
authors.lastname: Hino
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004052:Diethylnitrosamine; D015180:Electrophoresis, Gel, Two-Dimensional; D016166:Free Radical Scavengers; D006242:Haptoglobins / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000502:physiology; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D011233:Precipitin Tests; D013997:Time Factors
chemical_list: D002273:Carcinogens; D016166:Free Radical Scavengers; D006242:Haptoglobins; D037102:Lectins; D004052:Diethylnitrosamine; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase