Increased Protein Glycation in Cirrhosis and Therapeutic Strategies to Prevent It
Abstract
A bstract: 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.
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Alcohol ingestion enhances AGE synthesis and plasma AGEs in the circulation, especially in the portal and hepatic veins of cirrhotic livers; elevated AGE levels support AGE-protein adduct formation accompanied by decreased albumin turnover in plasma.
“Alcohol ingestion also enhances AGE synthesis and plasma AGEs in the circulation, especially in the portal and hepatic veins of cirrhotic livers.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [232]
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“Similar results of elevated production of AGE and its plasma levels in cirrhotic patients compared to those in healthy individuals were previously reported [194].”
Result
- Authors
- AHMED, N., LÜTHEN, R., HÄUSSINGER, D., ŠEBEKOVÁ, K., SCHINZEL, R., VOELKER, W., HEIDLAND, A., & THORNALLEY, P. J.
- Affiliations
- University of Essex (GB)
- Heinrich Heine University Düsseldorf (DE)
- University of Würzburg (DE)
- Corresponding author
- THORNALLEY, PAUL J.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2005-06
- Volume
- 1043
- Issue
- 1
- Pages
- 718-724
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W2156331698
- Cited by
- 26
- References
- 41
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 2
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- protein glycation, liver cirrhosis, dicarbonyl compounds, lipid peroxidation, reactive aldehydes, protein oxidation, nitrosation, albumin turnover, proteasome, plasma biomarkers, alcoholic liver disease, non-alcoholic liver disease, glutathione, thiamine therapy
- MeSH terms
- Blood Proteins, Glycosylation, Humans, Liver Cirrhosis, Reference Values, Glycation End Products, Advanced
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