Glycation of Human β2-Microglobulin in Patients with Hemodialysis-Associated Amyloidosis: Identification of the Glycated Sites

Toshio Miyata, Reiko Inagi, Yoshinao Wada, Yasuhiko Ueda, Yoshiyasu Iida, Motoko Takahashi, Naoyuki Taniguchi, Kenji Maeda

研究成果: Article査読

61 被引用数 (Scopus)

抄録

β2-Microglobulin (β2M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that β2M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified β2M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-α, interleukin-1 β, and interleukin-6 from macrophages, suggesting the potential link of glycation of β2M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of β2M purified from long-term hemodialysis patients as well as β2M incubated with glucose in vitro. Borotritide-treated β2M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of β2 formed in vivo were found to be almost the same as those of glycated β2M in vitro. The primary glycated site was the α-amino group of the amino terminal isoleucine. Other minor sites were the ϵ-amino groups of Lys-19, −41, −48, −58, −91, and −94. Computer graphics of the three-dimensional structure of β2M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.

本文言語English
ページ(範囲)12215-12221
ページ数7
ジャーナルBiochemistry
33
40
DOI
出版ステータスPublished - 1994 10月 1
外部発表はい

ASJC Scopus subject areas

  • 生化学

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