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

被引:10
作者
Ekuni, A [1 ]
Miyoshi, E [1 ]
Ko, JH [1 ]
Noda, K [1 ]
Kitada, T [1 ]
Ihara, S [1 ]
Endo, T [1 ]
Hino, A [1 ]
Honke, K [1 ]
Taniguchi, N [1 ]
机构
[1] Osaka Univ, Dept Biochem, Grad Sch Med, Suita, Osaka, Japan
关键词
GnT-III; DEN; hepatoma; haptoglobin; glycomics; mice;
D O I
10.1080/1071576021000005258
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-acetylglucosaminyl-transferase 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 E-4-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.
引用
收藏
页码:827 / 833
页数:7
相关论文
共 24 条
  • [21] Yang XP, 2000, CANCER RES, V60, P3313
  • [22] Yoshimura M, 1996, CANCER RES, V56, P412
  • [23] SUPPRESSION OF LUNG METASTASIS OF B16 MOUSE MELANOMA BY N-ACETYLGLUCOSAMINYLTRANSFERASE-III GENE TRANSFECTION
    YOSHIMURA, M
    NISHIKAWA, A
    IHARA, Y
    TANIGUCHI, S
    TANIGUCHI, N
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (19) : 8754 - 8758
  • [24] HIGH EXPRESSION OF UDP-N-ACETYLGLUCOSAMINE - BETA-D MANNOSIDE BETA-1,4-N-ACETYLGLUCOSAMINYLTRANSFERASE-III (GNT-III) IN CHRONIC MYELOGENOUS LEUKEMIA IN BLAST CRISIS
    YOSHIMURA, M
    NISHIKAWA, A
    IHARA, Y
    NISHIURA, T
    NAKAO, H
    KANAYAMA, Y
    MATUZAWA, Y
    TANIGUCHI, N
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1995, 60 (04) : 443 - 449