Glyoxalase biochemistry

Honek, John F.

doi:10.1515/bmc-2015-0025

Cited by 33 publications

(20 citation statements)

References 110 publications

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“…This enzyme is ubiquitously expressed in all mammalian cells and has been suggested as involved in cellular aging and death. The glyoxalase system protects cells by converting GO and MGO to D-lactate [ 29 , 30 ]. Bladder, breast, colon, lung, prostate and gastric tumours display increased GLO1 activity as one of the mutations processes observed during carcinogenesis [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells

Schmidt

Ferreira

Passos

et al. 2020

IJMS

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Breast cancer is the leading cause of cancer mortality in women worldwide. Conventional cancer treatment is costly and results in many side effects. Dietary bioactive compounds may be a potential source for breast cancer prevention and treatment. In this scenario, the aim of this study was to investigate the effects of the bioactive compounds resveratrol, curcumin and piperine (R-C-P) on MCF-7 breast cancer cells and to associate them to Glyoxalase 1 (GLO1) activity. The findings indicate that R-C-P exhibits cytotoxicity towards MCF-7 cells. R-C-P decreased mitochondrial membrane potential (ΔΨm) by 1.93-, 2.04- and 1.17-fold, respectively. Glutathione and N-acetylcysteine were able to reverse the cytotoxicity of the assessed bioactive compounds in MCF-7 cells. R-C-P reduced GLO1 activity by 1.36-, 1.92- and 1.31-fold, respectively. R-C-P in the presence of antimycin A led to 1.98-, 1.65- and 2.16-fold decreases in D-lactate levels after 2 h of treatment, respectively. Glyoxal and methylglyoxal presented cytotoxic effects on MCF-7 cells, with IC50 values of 2.8 and 2.7 mM and of 1.5 and 1.4 mM after 24 and 48 h of treatment, respectively. In conclusion, this study demonstrated that R-C-P results in cytotoxic effects in MCF-7 cells and that this outcome is associated with decreasing GLO1 activity and mitochondrial dysfunction.

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Section: Introductionmentioning

confidence: 99%

Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells

Schmidt

Ferreira

Passos

et al. 2020

IJMS

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“…Another important detoxification pathway in which GSH takes part as a cofactor is the glyoxalase system. It comprises two enzymes, namely glyoxalase I (Glx‐I) and glyoxalase II (Glx‐II), that sequentially catalyze the conversion of methylglyoxal (MG) to D‐lactate via the formation of a S‐D‐lactoylglutathione intermediate . Cells utilize the glyoxalase system to eliminate toxic α‐oxoaldehydes, especially methylglyoxal, thereby preventing α‐oxoaldehyde‐mediated formation of advanced glycation end‐products (AGEs) .…”

Section: Introductionmentioning

confidence: 99%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs. The balance between its concentration and redox state is due to a complex series of interactions between biosynthesis, utilization, degradation, and transport. All these factors are of great importance to understand the significance of cellular redox balance and its relationship with physiological responses and pathological conditions. The purpose of this review is to give an overview on glutathione cellular compartmentalization. Information on its subcellular distribution provides a deeper understanding of glutathione‐dependent processes and reflects the importance of compartmentalization in the regulation of specific cellular pathways. © 2018 BioFactors, 45(2):152–168, 2019

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“…The system consists of reduced glutathione (GSH) and two enzymes, the isomerase glyoxalase 1 (Glo1) and the thioesterase glyoxalase 2 (Glo2). Even though there are organelles and organisms with insular glyoxalases pointing to alternative functions [1] , [2] , [3] , Glo1 and Glo2 usually act together, for example, to catalyze the formation of d -lactate from glucose-derived methylglyoxal (MG) [1] , [2] , [3] , [4] , [5] . The glyoxalase system in humans prevents the accumulation of MG and of MG-derived advanced glycation end products (AGEs) with implications for numerous pathophysiological conditions including diabetes and cancer [6] , [7] , [8] , [9] .…”

Section: Introductionmentioning

confidence: 99%

Hemolytic and antimalarial effects of tight-binding glyoxalase 1 inhibitors on the host-parasite unit of erythrocytes infected with Plasmodium falciparum

et al. 2016

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Glyoxalases prevent the formation of advanced glycation end products by converting glycolysis-derived methylglyoxal to d-lactate with the help of glutathione. Vander Jagt and colleagues previously showed that erythrocytes release about thirty times more d-lactate after infection with the human malaria parasite Plasmodium falciparum. Functional glyoxalases in the host-parasite unit might therefore be crucial for parasite survival. Here, we determined the antimalarial and hemolytic activity of two tight-binding glyoxalase inhibitors using infected and uninfected erythrocytes. In addition, we synthesized and analyzed a set of diester derivates of both tight-binding inhibitors resulting in up to threefold lower IC50 values and an altered methemoglobin formation and hemolytic activity depending on the type of ester. Inhibitor treatments of uninfected erythrocytes revealed an extremely slow inactivation of the host cell glyoxalase, irrespective of inhibitor modifications, and a potential dispensability of the host cell enzyme for parasite survival. Our study highlights the benefits and drawbacks of different esterifications of glutathione-derived inhibitors and demonstrates the suitability of glyoxalase inhibitors as a tool for deciphering the relevance and mode of action of different glyoxalase systems in a host-parasite unit.

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Glyoxalase biochemistry

Cited by 33 publications

References 110 publications

Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells

Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

Hemolytic and antimalarial effects of tight-binding glyoxalase 1 inhibitors on the host-parasite unit of erythrocytes infected with Plasmodium falciparum

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