肝脏发生的蛋白质糖基化、氧化和亚硝化过程与纤维化的作用

来源 :世界核心医学期刊文摘(胃肠病学分册) | 被引量 : 0次 | 上传用户:wyfwin
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Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also undergo hepatic extraction. We investigated the hepatic extraction of glycated, oxidised and nitrosated proteins in vivo. Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry. There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in the concentrations of fructosyl-lysine and advanced glycation endproduct residues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation. We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects. Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also conducted hepatic extraction. We investigated the hepatic extraction of glycated, oxidized and nitrosated proteins in vivo. Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry. There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extract of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in concentration of the concentrations of fructosyl-lysine and advanced glycation endproduct resid ues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation. We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects.
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