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: Yoshihiro Kamada, Sachiho Kida, Ken-Ichi Hirano, Satoshi Yamaguchi, Akira Suzuki, Chikako Hashimoto, Akihiro Kimura, Motoya Sato, Hironobu Fujii, Tomoaki Sobajima, Akiko Yamamoto, Yusuke Ebisutani, Shinji Takamatsu, Shinichiro Shinzaki, Yuichi Yoshida, Makoto Yamada, Hironori Nagasaka, Tetsuo Takehara, Eiji Miyoshi
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 311 Issue 5 Pg. G859-G868 (11 01 2016) ISSN: 1522-1547 [Electronic] United States
• PMID: 27659420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• ATP Binding Cassette Transporter 1
• Apolipoproteins A
• Lipoproteins, HDL
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase

Topics

• ATP Binding Cassette Transporter 1 (metabolism)
• Animals
• Apolipoproteins A (metabolism)
• Cell Line, Tumor
• Female
• Glycosylation
• Humans
• Lipoproteins, HDL (metabolism)
• Liver (metabolism)
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• N-Acetylglucosaminyltransferases (metabolism)
• Phosphorylation