title: Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly.
abstract: Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing β1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mice. ApoAI and ABCA1 were also significantly elevated in GnT-V transfectants compared with mock-transfected cells. Moreover, ApoAI protein in the cultured media of GnT-V transfectants was significantly increased. Finally, we found a strong correlation between serum GnT-V activity and HDL-C concentration in human subjects. Multivariate logistic analyses demonstrated that GnT-V activity was an independent and significant determinant for serum HDL-C levels even adjusted with age and gender differences. Further analyses represented that serum GnT-V activity had strong correlation especially with the large-size HDL particle concentration. These findings indicate that enhanced hepatic GnT-V activity accelerated HDL assembly and could be a novel mechanism for HDL synthesis.
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Sachiho
authors.initials: S
authors.lastname: Kida
authors.affiliation: Laboratory of Cardiovascular Disease, Novel, Non-invasive and Nutritional Therapeutics, Osaka University, Suita, Osaka, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hirano
authors.affiliation: Laboratory of Cardiovascular Disease, Novel, Non-invasive and Nutritional Therapeutics, Osaka University, Suita, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Cardiovascular Disease, Novel, Non-invasive and Nutritional Therapeutics, Osaka University, Suita, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Laboratory of Cardiovascular Disease, Novel, Non-invasive and Nutritional Therapeutics, Osaka University, Suita, Osaka, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Hashimoto
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Motoya
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sobajima
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ebisutani
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takamatsu
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.|Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: aMs New Otani Clinic, Osaka, Osaka, Japan; and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Takarazuka City Hospital, Takarazuka, Hyogo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; emiyoshi@sahs.med.osaka-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006031:Glycosylation; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
keywords: ABCA1; ApoAI; GnT-V; high-density lipoprotein; liver