Glo1

Case Study 1: Fabiola Garcia Cortizo, 2022

Methylglyoxal (MG) is a highly reactive α-oxoaldehyde that glycates proteins. MG has been linked to the development of diabetic complications: MG is the major precursor of advanced glycation end products (AGEs), a risk marker for diabetic complications in humans. MG is detoxified in large part through the glyoxalase system, whose rate-limiting enzyme is glyoxalase I (Glo1). Hence, the researchers aimed to study how Glo1 activity is regulated. They studied the regulation and effect of post-translational modifications of Glo1 in tissue culture and in mouse models of diabetes.

The results show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. They find that Glo1 Y136 phosphorylation responds in a bimodal fashion to glucose levels, increasing in cell culture from 0 mM to 5 mM (physiological) glucose, and then decreasing at higher glucose concentrations, both in cell culture and in mouse models of hyperglycemia. These data elevated MG leads to hyperglycemia, suggest the existence of a deleterious positive feedback loop whereby hyperglycemia leads to reduced Glo1 activity, contributing to elevated MG levels, which in turn promote hyperglycemia.

Fig1. Mutation of Glo1 Y136 to alanine reduces Glo1 activity.

Fig2. Multiple different kinases can phosphorylate Glo1 Y136 in an in vitro kinase assay, including members of the Src family.

Case Study 2: Tomonori Hara, 2021

Carbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, the researchers found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger.

Fig3. Western blot of WT- and GLO1 KO-hiPSCs using an antibody against GLO1.

Fig4. Plot of OCR in WT- and GLO1 KO-hiPSCs versus measurement time.

Fig1. Glyoxalase I (GLO1) regulating tumor cell survival and proliferation. (Xiaofang Geng, 2014)

Fig2. Glyoxalase 1 (Glo1) sustains the metastatic phenotype of prostate cancer cells via epithelial-to-mesenchymal transition (EMT) control. (Cinzia Antognelli, 2018)

Glo1 involved in several pathways and played different roles in them. We selected most pathways Glo1 participated on our site, such as Pyruvate metabolism, which may be useful for your reference. Also, other proteins which involved in the same pathway with Glo1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Glo1 has several biochemical functions, for example, lactoylglutathione lyase activity, zinc ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Glo1 itself. We selected most functions Glo1 had, and list some proteins which have the same functions with Glo1. You can find most of the proteins on our site.

Glo1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Glo1 here. Most of them are supplied by our site. Hope this information will be useful for your research of Glo1.

IKBKE; MAP3K13; IKBKG; MAP1LC3B