Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are
responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as
a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts
(AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors,
resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation.
This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and
hepatocellular carcinoma (HCC). AGEs and RAGE are upregulated in liver fibrosis, and the silencing
of RAGE reduced collagen deposition and the tumor growth of HCC. Nevertheless, data relating to
Glo-I in fibrosis and cirrhosis are preliminary. Glo-I expression was found to be reduced in early and
advanced cirrhosis with a subsequent increase of MGO-levels. On the other hand, pharmacological
modulation of Glo-I resulted in the reduced activation of hepatic stellate cells and therefore reduced
fibrosis in the CCl4-model of cirrhosis. Thus, current research highlighted the Glo-I/AGE/RAGE
system as an interesting therapeutic target in chronic liver diseases. These findings need further
elucidation in preclinical and clinical studies.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88759 |
| Date | 22 December 2023 |
| Creators | Hollenbach, Marcus |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2466, 10.3390/ijms18112466 |
Page generated in 0.0019 seconds