Increased protein glycation in cirrhosis and therapeutic strategies to prevent it.
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.
Ahmed
Naila
N
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
Lüthen
Reinhard
R
Häussinger
Dieter
D
Sebeková
Katarína
K
Schinzel
Reinhard
R
Voelker
Wolfram
W
Heidland
August
A
Thornalley
Paul J
PJ
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
D001798:Blood Proteins; D017127:Glycation End Products, Advanced