Imidazolium crosslinks derived from reaction of lysine with glyoxal and methylglyoxal are increased in serum proteins of uremic patients: evidence for increased oxidative stress in uremia

FEBS Letters

Shinzato, Toru¹  Brinkmann Frye, Elisabeth²  Usami, Jun¹  Maeda, Kenji¹  Matsumoto, Yoshihiro¹  Baynes, John W²  Odani, Hiroko¹ 

[1] Department of Internal Medicine, Daiko Medical Center, Nagoya University, 1-1-20 Daiko-minami, Higashi-ku, Nagoya 461-0073, Japan;Departments of Ophthalmology and Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA

关键词: Advanced glycation end product;    Crosslink;    Glyoxal;    Imidazole;    Maillard reaction;    Methylglyoxal;    AGE;    advanced glycation end product;    ALE;    advanced lipoxidation end product;    GO;    glyoxal;    MGO;    methylglyoxal;    GOLD;    glyoxal-derived di-lysine imidazolium crosslink;    MOLD;    methylglyoxal-derived di-lysine imidazolium crosslink;    ESI;    electrospray ionization;    MS;    mass spectrometry;    SIM;    selected ion monitoring;    CEL;    N ϵ-(carboxyethyl)lysine;    CML;    N ϵ-(carboxymethyl)lysine;    fL;    formyllysine;   

DOI  :  10.1016/S0014-5793(98)00416-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed during autoxidation of both carbohydrates and lipids. They may react with lysine and arginine residues of proteins in Maillard or browning reactions, yielding advanced glycation or lipoxidation end products. Among these are the imidazolium crosslinks, N,N(-di(N ^ϵ-lysino))imidazolium (glyoxal-lysine dimer, GOLD) and N,N(-di(N ^ϵ-lysino))-4-methyl-imidazolium (methylglyoxal-lysine dimer, MOLD). We have detected and measured GOLD and MOLD in human serum by electrospray ionization/mass spectrometry/mass spectrometry (ESI/MS/MS), using ¹⁵N₄-GOLD and ¹⁵N₄-MOLD as internal standards. In this report we show that levels of GOLD and MOLD are significantly elevated (3–4-fold, P<0.01) in sera of non-diabetic uremic patients, compared to age-matched controls, and represent a major class of non-enzymatic, Maillard reaction crosslinks in plasma proteins. These results provide strong evidence for increased non-enzymatic crosslinking of tissue proteins by GO and MGO in uremia, implicating oxidative stress and resultant advanced glycation and lipoxidation reactions in tissue damage in uremia.

【 授权许可】

Unknown