title: Increased protein glycation in cirrhosis and therapeutic strategies to prevent it.
abstract: Glycation of liver proteins by reactive aldehydes formed from the metabolism of ethanol and lipid peroxidation has been implicated in the development of both alcoholic and nonalcoholic liver cirrhosis. Modified proteins are targeted to the proteasome for proteolysis. Release of glycation-free adducts into the circulation may provide a diagnostic "signature" of hepatic protein damage. We quantitatively screened protein glycation, oxidation, and nitrosation adduct residues and free adducts in portal, hepatic, and peripheral venous blood plasma of cirrhotic patients; we also screened the hepatic and peripheral venous blood plasma of control subjects by liquid chromatography-mass spectrometry. There was a remarkable 14-16-fold increase of glyoxal-derived, hydroimidazolone-free adduct in portal and hepatic venous plasma of cirrhotic patients with respect to normal controls. There was only a twofold increase of glycation adduct residues in plasma proteins in cirrhotic patients, which was attributed mainly to decreased albumin turnover. Therapeutic strategies to decrease dicarbonyl compounds may be beneficial, such as dicarbonyl scavengers, glutathione repleting agents, and high-dose thiamine therapy.
authors.affiliation: Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
authors.forename: Naila
authors.initials: N
authors.lastname: Ahmed
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lüthen
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Katarína
authors.initials: K
authors.lastname: Sebeková
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schinzel
authors.forename: Wolfram
authors.initials: W
authors.lastname: Voelker
authors.forename: August
authors.initials: A
authors.lastname: Heidland
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D012016:Reference Values
chemical_list: D001798:Blood Proteins; D017127:Glycation End Products, Advanced