Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage

Abstract

The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs. MGO and its advanced glycated end products (AGEs) are associated with age-related diseases including diabetes, vascular dysfunction and neurodegeneration. Endothelial dysfunction is the first step in the initiation, progression and clinical outcome of vascular complications, such as retinopathy, nephropathy, impaired wound healing and macroangiopathy. Because of these considerations, studies have been centered on understanding the molecular basis of endothelial dysfunction in diabetes, unveiling a central role of MGO-Glo1 imbalance in the onset of vascular complications. This review focuses on the current understanding of MGO accumulation and Glo1 activity in diabetes, and their contribution on the impairment of endothelial function leading to diabetes-associated vascular damage.

Cinnamaldehyde protects from methylglyoxal‐induced vascular damage: Effect on nitric oxide and advanced glycation end products

“…Results are expressed as mean ± SE of mean (n = 3). # shows a significant difference (<0.05) when compared to control, *shows a significant difference (<0.05) when compared to MG vascular dysfunction among other complications, such as aging and hypertension (Nigro et al, 2017;Vulesevic et al, 2016). El-Bassossy et al (2016) even went on to argue that MG is responsible for an amplified contractile response similar to that observed in diabetes.…”

“…Such vascular dysfunction is mostly characterized by an amplified vascular contraction which consequently hinders complete vasodilation (Bahia et al, ). The use of MG to study such vascular complications is justified by recent studies claiming that MG accumulation in the body is associated with vascular dysfunction among other complications, such as aging and hypertension (Nigro et al, ; Vulesevic et al, ). El‐Bassossy et al () even went on to argue that MG is responsible for an amplified contractile response similar to that observed in diabetes.…”

Glycine increases glyoxalase‐1 function by promoting nuclear factor erythroid 2‐related factor 2 translocation into the nucleus of kidney cells of streptozotocin‐induced diabetic rats

“…Once formed, AGEs can activate the receptor for AGEs (RAGE), thus triggering a vicious loop of inflammation and oxidative stress, which eventually leads to renal damages. Recent findings suggest that methylglyoxal (MG), a highly‐reactive byproduct of glycolysis, is much more potent than glucose in promoting the formation of AGEs and in activating the AGE/RAGE signaling pathway.…”

Effect of prednisolone on glyoxalase 1 in an inbred mouse model of aristolochic acid nephropathy using a proteomics method with fluorogenic derivatization-liquid chromatography-tandem mass spectrometry

“…GLO1, the rate-limiting enzyme, spontaneously catalyses the conversion of methylglyoxal-GSH hemithioacetal into thioester S-D-lactoylglutathione [39]. This step is the most important in metabolism of methylglyoxal into Dlactate [39,40]. GLO2 metabolizes S-D-lactoylglutathione to D-lactate and GSH.…”