Hypoxic regulation of glycosylation via the N-acetylglucosamine cycle

Ken Shirato, Kazuki Nakajima, Hiroaki Korekane, Shinji Takamatsu, Congxiao Gao, Takashi Angata, Kazuaki Ohtsubo, Naoyuki Taniguchi

研究成果: Review article査読

43 被引用数 (Scopus)

抄録

Glucose is an energy substrate, as well as the primary source of nucleotide sugars, which are utilized as donor substrates in protein glycosylation. Appropriate glycosylation is necessary to maintain the stability of protein, and is also important in the localization and trafficking of proteins. The dysregulation of glycosylation results in the development of a variety of disorders, such as cancer, diabetes mellitus and emphysema. Glycosylation is kinetically regulated by dynamically changing the portfolio of glycosyltransferases, nucleotide sugars, and nucleotide sugar transporters, which together form a part of what is currently referred to as the "Glycan cycle". An excess or a deficiency in the expression of glycosyltransferases has been shown to alter the glycosylation pattern, which subsequently leads to the onset, progression and exacerbation of a number of diseases. Furthermore, alterations in intracellular nucleotide sugar levels can also modulate glycosylation patterns. It is observed that pathological hypoxic microenvironments frequently occur in solid cancers and inflammatory foci. Hypoxic conditions dramatically change gene expression profiles, by activating hypoxia-inducible factor-1, which mediates adaptive cellular responses. Hypoxia-induced glycosyltransferases and nucleotide sugar transporters have been shown to modulate glycosylation patterns that are part of the mechanism associated with cancer metastasis. Hypoxia-inducible factor-1 also induces the expression of glucose transporters and various types of glycolytic enzymes, leading to shifts in glucose metabolic patterns. This fact strongly suggests that hypoxic conditions are an important factor in modulating various nucleotide sugar biosynthetic pathways. This review discusses some of the current thinking of how hypoxia alters glucose metabolic fluxes that can modulate cellular glycosylation patterns and consequently modify cellular functions, particularly from the standpoint of the N-acetylglucosamine cycle, a part of the "Glycan cycle".

本文言語English
ページ(範囲)20-25
ページ数6
ジャーナルJournal of Clinical Biochemistry and Nutrition
48
1
DOI
出版ステータスPublished - 01-2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 栄養および糖尿病
  • 臨床生化学

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