title: 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.
abstract: 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(epsilon)-lysino))imidazolium (glyoxal-lysine dimer, GOLD) and N,N(-di(N(epsilon)-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.
authors.affiliation: Department of Internal Medicine, Daiko Medical Center, Nagoya University, Japan. hirokood@med.nagoya-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Odani
authors.forename: T
authors.initials: T
authors.lastname: Shinzato
authors.forename: J
authors.initials: J
authors.lastname: Usami
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: E
authors.initials: E
authors.lastname: Brinkmann Frye
authors.forename: J W
authors.initials: JW
authors.lastname: Baynes
authors.forename: K
authors.initials: K
authors.lastname: Maeda
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry*; D005260:Female; D006037:Glyoxal / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications; D008239:Lysine / Q000097:blood* / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000097:blood* / Q000737:chemistry; D014511:Uremia / Q000097:blood* / Q000150:complications
chemical_list: D003432:Cross-Linking Reagents; D007093:Imidazoles; D006037:Glyoxal; D011765:Pyruvaldehyde; D008239:Lysine