Characterization of glyoxalase 1 deficient mice

Abstract

Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme in the Glyoxalase system, a metabolic pathway that detoxifies methylglyoxal (MG). Methylglyoxal, a cytotoxic byproduct of glycolysis, is formed by degradation of the glycolytic intermediates dihydroxyacetone, phosphate, and glyceraldehyde-3-phosphate. This byproduct induces oxidative stress, apoptosis, nucleotide modification, and protein modification, forming advanced glycation end products (AGEs). To alleviate MG’s cytotoxic effects, GLO1 uses glutathione as a cofactor to enzymatically convert MG into d-lactate, which is a less reactive substance. In addition, recent findings have linked GLO1 to psychiatric diseases, such as, depression, schizophrenia, and autism. In the research for this paper, knockout GLO1 mice were generated and used to perform various characterization tests. The GLO1 knockout mice showed reduced levels of MG compared to wild-type, heterozygous mice. Moreover, GLO1 knockout mice showed an absence of GLO1 activity, decreased level of lactates, and higher levels of AGE formation. Finally, we showed that there is a positive correlation between GLO1 and anxiety-like behavior via two behavior tests: Open field and Light-dark box test.