Search Results (214)

Glyoxalase I (GLYI) is the key regulatory enzyme in the glyoxalase pathway. This pathway enables plants to neutralize methylglyoxal (MG) using glutathione (GSH), a mechanism significant for their acclimation to environmental stress. While functionally significant, the specific functions of GLYI genes in Amaranthus palmeri remain unexplored. In this study, integrated bioinformatics and expression analysis was used to identify five GLYI genes in A. palmeri. The results indicate that ApGLYI proteins are hydrophilic and slightly acidic, localized to scaffolds 1, 11, 13, and 16 of the A. palmeri genome. Phylogenetic analysis grouped ApGLYIs with other plant GLYI proteins into three distinct clades, each exhibiting conserved motif patterns. Expression analyses demonstrate that ApGLYI genes participate in both early and late regulatory phases of MG detoxification and signaling, responding to diverse stimuli including high temperature, NaCl, osmotic stress, exogenous methylglyoxal, abscisic acid (ABA), and methyl jasmonate (MeJA). Conversely, glufosinate ammonium treatment appears to compromise this cellular detoxification system. These results offer the evolutionary trajectory and functional significance of the ApGLYI gene. They establish a foundation for subsequent studies toward managing A. palmeri infestation and using these genes to improve stress resilience in cultivated crops through breeding strategies. Full article

Plastics have emerged as a significant pollutant, posing a serious threat to the sustainability of the soil ecosystem and food security because of their long-term persistence, resilience, and robustness under different environmental conditions. The present investigation explored the impact of different doses of polypropylene (PP) on lentil plants and attenuation of the adverse impacts of PP by the application of pineapple fruit peel biochar (PBC). Lentil (Lens culinaris) plants exposed to PP treatment reduced morphological traits and relative water contents, reflecting photosynthetic injuries, a rise in lipid peroxidation, and electrolyte leakage. Utilization of PBC derived from waste biomass enhanced the growth attributes of lentils and alleviated PP-incited oxidative stress impacts. Polypropylene stress enhanced oxidative stress and increased enzymatic and non-enzymatic antioxidant variables in lentil plants. Antioxidant enzymes superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, and glyoxalase enzymes were markedly upregulated in lentil after PBC amendment in PP3-treated soil. There was a significant reduction in methylglyoxal content by the activities of glyoxylase enzymes, minimizing the negative impacts of PP. Therefore, soil amendment with PBC protected lentil plants from PP-instigated oxidative disruption by modulating activities of antioxidant defense and glyoxalase system. Production of PBC from biomass wastes results in a safe, cost-effective, and ecofriendly material that can be used at the industrial level for the cultivation of crops in PP-contaminated soil. The novelty of the present research lies in promoting soil management practices and fostering our understanding of waste materials reutilization as renewable assets to combat the ecological implications of plastic pollution, and it emphasizes the treatment of plastic wastes with other waste materials and their practical applications to overcome plastic pollution. Full article

Glyoxalase 2 (Glo2) is a key enzyme of the glyoxalase system that catalyzes the conversion of S-lactoylglutathione (LSG) into glutathione (GSH) and D-lactate. In prostate cancer (PCa), we previously demonstrated that the oncogenic PTEN-PI3K–AKT–mTOR–ERα signaling pathway upregulates Glo2, leading to intracellular D-lactate accumulation and enhanced cell migration, invasiveness, and expression of epithelial-to-mesenchymal transition (EMT)-associated markers. However, whether D-lactate acts as a bioactive metabolic signal contributing to tumor aggressiveness remains unclear. Here, after confirming our previous findings, we demonstrate—using Glo2 silencing, ectopic expression, pharmacological inhibitors, and exogenous D-lactate supplementation—that Glo2-dependent D-lactate accumulation promotes EMT-like plasticity, migration, and invasion in PTEN-deficient PCa cells via a functional link with FAK/Src signaling. Collectively, these results suggest that the Glo2–D-lactate axis may contribute to metabolic rewiring associated with aggressive behavior in PTEN-deficient PCa, warranting further in vivo studies to evaluate its potential as a therapeutic target to limit tumor progression. Full article

Citrus trees are mainly cultivated in acidic soils. Excessive manganese (Mn) is the second most limiting factor for crop productivity in acidic soils after aluminum toxicity. The roles of reactive oxygen species (ROS) and methylglyoxal (MG) detoxification systems in augmented pH-mediated amelioration of excessive Mn are poorly understood. ‘Sour pummelo’ (Citrus grandis (L.) Osbeck) seedlings were exposed to nutrient solution at a Mn concentration of 500 (Mn500) or 2 (Mn2) μM and a pH of 3 (P3) or 5 (P5). The increase in pH attenuated Mn500-induced increases in ROS production and MG and malondialdehyde accumulation in roots and leaves. Additionally, the increase in pH enhanced the coordinated detoxification capability of both ROS and methylglyoxal scavenging systems in these tissues under Mn500. These findings corroborated the hypothesis that augmenting pH enhances the capability of these tissues to detoxify ROS and methylglyoxal under Mn excess. Therefore, this study provided new evidence on the roles of ROS and MG detoxification systems in the augmented pH-mediated amelioration of oxidative damage in ‘Sour pummelo’ leaves and roots caused by Mn excess, as well as a basis for correcting Mn toxicity by augmenting soil pH. Full article

Glyoxal (GO) and methylglyoxal (MGO) are highly toxic metabolic byproducts that induce carbonyl stress in bacteria and eukaryotes. Their accumulation in cells is linked to non-enzymatic glycosylation (glycation) of proteins, nucleic acids, and lipids, leading to the formation of advanced glycation end products (AGEs). In humans, AGEs are associated with several health problems, such as diabetes, Alzheimer’s disease, cancer, and aging. Recent studies indicate that, despite their short lifespan, bacteria are also affected by AGEs formation. In this review, we summarize the pathways and mechanisms that help bacteria cope with GO, MGO, and AGEs. We also discuss the impact of dietary AGEs on gut microbiota and the antibacterial activity of host-derived GO/MGO. Recent studies highlight three main areas for future research: the role of AGEs in dysbiosis, the regulation of protein activities by MGO/GO-dependent modifications, and the potential use of glyoxalase pathway inhibitors to combat pathogens. This last point is especially important due to the rising prevalence of multidrug-resistant strains and the failure of antibiotic therapies. Full article

Drought stress (DS) is a primary environmental factor that limits the production of ginger (Zingiber officinale Roscoe). Silica nanoparticles (SiNPs) have been shown to enhance drought resistance in ginger by modulating water relations. However, the specific impact of SiNPs on the antioxidant and glyoxalase system responses to DS remains unclear. To investigate the impact of SiNP100 on photosynthetic and antioxidant metabolism in ginger under DS, four treatments were designed in this study: control (CK), drought stress (DS), silica nanoparticles (SiNP100) application, and the combined treatment of DS and SiNP100 (DS + SiNP100). The results showed that SiNP100 alleviated DS-induced damage by improving photosynthetic parameters, chlorophyll content, and the efficiency of photosystems I and II. DS significantly increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and methylglyoxal (MG), thereby inducing oxidative stress. SiNP100 mitigated this effect by reducing ROS accumulation and enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Furthermore, SiNP100 boosted the ascorbate–glutathione (AsA-GSH) cycle by increasing the activities of key enzymes (APX, DHAR, MDHAR, and GR) and upregulating the expression of ZoDHAR2, ZoAPX1, and ZoGR2. This leads to higher ascorbate and glutathione levels in ginger. SiNP100 also bolstered the glyoxalase system, as evidenced by increased activities of glyoxalase I (Gly I) and glyoxalase II (Gly II), alongside the upregulation of ZoGLY1 expression, thereby promoting methylglyoxal (MG) detoxification. In conclusion, SiNP100 enhances drought tolerance in ginger by reinforcing the antioxidant defense system, AsA-GSH cycle, and methylglyoxal detoxification system, thereby protecting photosynthetic metabolism and promoting growth. Full article

Although the antioxidant role of melatonin in stress mitigation is well established, its multifunctionality may support plant tolerance to drought through additional mechanisms. This study aimed to evaluate melatonin’s contribution to both antioxidant defence and methylglyoxal (MG) detoxification—a harmful compound that disrupts cellular balance under drought stress. The glyoxalase pathway, which is aided by glutathione, plays a pivotal role in MG detoxification. Therefore, we examined the impact of both endogenous and exogenous melatonin on this system. Two pepper genotypes differing in drought tolerance and endogenous melatonin levels were exposed to 12 days of drought following a 5 µM melatonin treatment. The drought-tolerant genotype, characterized by higher levels of endogenous melatonin, exhibited more efficient MG detoxification through increased glutathione and glyoxalase activities, reduced membrane damage and enhanced antioxidant capacity. Exogenous melatonin further mitigated the effects of drought by reducing MG accumulation and stimulating antioxidant and glyoxalase enzymes. Overall, both endogenous and applied melatonin enhances drought tolerance in pepper by activating antioxidant defences and the glyoxalase pathway. Full article

Background: Advanced glycation end products (AGEs) and receptors for AGEs (RAGE) have been extensively implicated in metabolic and neurodegenerative disorders due to their capacity to alter protein structure and function through non-enzymatic glycation. More recently, methylglyoxal (MG), a highly reactive glycolytic byproduct, has gained attention as a critical mediator of AGE formation and an independent contributor to cellular distress, particularly in the context of diabetes mellitus and Alzheimer’s disease. Objectives: This review synthesizes evidence from experimental and clinical studies addressing MG generation and metabolism in brain tissue, emphasizing the glyoxalase system as the primary detoxification mechanism, the functional contribution of astrocytes, and the downstream consequences of MG accumulation. In addition, we examined the interplay between MG, RAGE signaling, unfolded protein response, and regulatory mechanisms involving the hexosamine biosynthesis pathway and O-GlcNAcylation of key proteins in glucose metabolism and insulin signaling. Results and Conclusions: Brain glucose hypometabolism is a consequence of insulin resistance and results in a metabolic rearrangement that expands the glycolytic pathway and generates more MG, which, in turn, can affect insulin signaling, further compromising the molecular basis of insulin resistance and creating a vicious cycle. Astrocytes are key cells in the generation and detoxification of MG in the brain, making them a therapeutic target. Full article

Deoxynivalenol (DON) is a trichothecene mycotoxin produced by Fusarium species that frequently contaminates cereal crops, representing a major threat to food safety, public health, and agricultural productivity. Its remarkable chemical stability during food processing presents significant challenges for effective detoxification. Among the available mitigation strategies, biological approaches have emerged as particularly promising, as they exploit enzymatic systems capable of converting DON into metabolites with substantially reduced toxicity. In this study, we provide a comprehensive analysis of the structural and evolutionary mechanisms underlying DON detoxification across three kingdoms of life. We investigated the fungal glutathione S-transferase Fhb7, the bacterial DepA/DepB epimerization pathway, and the plant SPG glyoxalase using integrative bioinformatics, phylogenetics, molecular modeling, and docking simulations. The selected enzymatic systems employ distinct yet complementary strategies: Fhb7 conjugates DON with glutathione and disrupts its epoxide ring, DepA/DepB converts it into the less toxic 3-epi-DON through stereospecific epimerization, and SPG glyoxalase mediates DON isomerization. Despite their mechanistic differences, these enzymes share key adaptive features that enable efficient DON recognition and detoxification. This work provides an integrative view of cross-kingdom enzymatic strategies for DON degradation, offering insights into their evolution and functional diversity. These findings open avenues for biotechnological applications, including the development of DON-resistant crops and innovative solutions to reduce mycotoxin contamination in the food chain. Full article

The glyoxalase pathway intermediate S-d-lactoylglutathione was recently implicated in protein post-translational modifications in animal systems. Here, we examined the spontaneous modification of the Arabidopsis thaliana cytosolic glyceraldehyde-3-phosphate dehydrogenase C1 (GAPC1) by this compound. Incubation of GAPC1 with S-d-lactoylglutathione resulted in the inhibition of enzyme activity. The inhibitory effect was concentration dependent and increased at alkaline pHs. Furthermore, the inhibition of GAPC1 by S-d-lactoylglutathione was favored by oxidative conditions and reversed by reduction with dithiothreitol. Analyses of the S-d-lactoylglutathione-treated protein by nanoLC-MS/MS revealed S-glutathionylation of its two Cys residues and N-lactoylation of six Lys residues. Protein structure predictions showed that the double S-glutathionylation is accommodated by the GAPC1 catalytic pocket, which likely explains enzyme inhibition. N-lactoylated sites overlap partially with previously reported N-acetylated sites at the surface of the GAPC1 tetramer. The efficiency of cytosolic glutaredoxin and thioredoxin isoforms was tested for reversing the S-d-lactoylglutathione-induced modification. In these assays, recovery of GAPC1 activity after inhibition by S-d-lactoylglutathione treatment was used as indicator of efficiency. The results show that both types of redoxins were able to reverse inhibition. We propose a model describing the mechanisms involved in the two types of post-translational modifications found on GAPC1 following exposure to S-d-lactoylglutathione. The possible involvement of these findings for the control over glycolytic metabolism is discussed. Full article

Background/Objectives: Diabetes mellitus is a metabolic disorder, and hyperglycemia results in abnormal brain function. Since glycolysis is the main energy pathway in glial cells, astrocytes possess a more developed glyoxalase (Glo) system than neurons and exhibit better survival. Glycolysis helps to protect glia from (i) dicarbonyl stress and (ii) formation of advanced glycation end products (AGEs). Since aminoguanidine (AG) is an inhibitor of AGE production, the purpose of this study was to determine the role of AG in crucial astrocytic proteins, such as Kir4.1, Glo1, and Glo2, in hyperglycemic conditions. Methods: We cultured astrocytes in normal (5 mM)- and high (25 mM)-glucose conditions. After two weeks, we seeded the cells in six-well plates, with 300,000 cells/well, and then treated them with 9 mM of AG for 24 h. Results: Expression of the glyoxalases Glo1 and Glo2, and of Kir4.1, is decreased in hyperglycemic conditions; however, treatment with AG recovers the expression of the Kir4.1 protein as well as the inward currents of hyperglycemic astrocytes. Conclusion: We demonstrated that regulation of the glyoxalase system via AG or another scavenger of carbonyl and aldehydes containing polyamine groups can contribute to the recovery of astrocyte function in diabetic patients. Full article

Glyoxalase 1 (Glo1) functions as a catalyst that neutralizes methylglyoxal (MG), a highly reactive glycating agent predominantly produced during glycolysis—a metabolic pathway upregulated in cancer cells. MG primarily reacts with the amino groups of proteins (especially at arginine residues), leading to the formation of a major advanced glycation end product known as MG-derived hydroimidazolone 1 (MG-H1). We previously demonstrated in PC3 human prostate cancer (PCa) cells that the PTEN/PKM2/ERα axis promotes their aggressive phenotype by regulating the Glo1/MG-H1 pathway. In this study, after confirming our earlier findings, we investigated the downstream mechanisms of the PTEN/PKM2/ERα/Glo1/MG-H1 axis in controlling PC3 cell growth, focusing on the role of RAGE, a high-affinity receptor for MG-H1; hydrogen peroxide (H₂O₂); and Krev interaction trapped 1 (KRIT1), an emerging tumor suppressor. Using genetic approaches and specific inhibitors/scavengers, we demonstrated that the PTEN/PKM2/ERα/Glo1/MG-H1 axis promotes PC3 cell growth—measured by proliferation and etoposide-induced apoptosis resistance—through a mechanism involving MG-H1/RAGE pathway desensitization that leads to H₂O₂-mediated KRIT1 downregulation. These findings support and expand the role of PTEN signaling in PCa progression and shed light on novel mechanistic pathways driven by MG-dependent glycative stress, involving KRIT1, in this still incurable stage of the disease. Full article

Catalase, a pivotal antioxidant enzyme, plays a central role in converting hydrogen peroxide (H₂O₂) into oxygen and water, thereby safeguarding cells from oxidative damage. In patients with diabetes, obesity, Alzheimer’s disease (AD), and Parkinson’s disease (PD), catalase becomes increasingly susceptible to non-enzymatic glycation, resulting in enzyme inactivation, oxidative stress, and defective mitochondrial function. This review uniquely emphasizes catalase glycation as a converging pathological mechanism that bridges metabolic and neurodegenerative disorders, underscoring its translational significance beyond prior general reviews on catalase function. In patients with metabolic diseases, glycation impairs β-cell function and insulin signaling, while in patients with neurodegeneration, it accelerates protein aggregation, mitochondrial dysfunction, and neuroinflammation. Notably, the colocalization of glycated catalase with amyloid-β and α-synuclein highlights its potential role in protein aggregation and neuronal toxicity, a mechanism not previously addressed. Therapeutically, targeting catalase glycation opens up new avenues for intervention. Natural and synthetic agents can be used to protect catalase activity by modulating glyoxalase activity, heme integrity, or carbonyl stress. Vitamins C and E, along with agents like sulforaphane and resveratrol, exert protection through complementary mechanisms, beyond ROS scavenging. Moreover, novel strategies, including Nrf2 activation and receptor for advanced glycation end products (RAGE) inhibition, are showing promise in restoring catalase activity and halting disease progression. By focusing on glycation-specific mechanisms and proposing targeted therapeutic approaches, this review positions catalase glycation as a novel and clinically relevant molecular target in patients with chronic diseases and a viable candidate for translational research aimed at improving clinical outcomes. Full article

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders among the elderly. The exact etiology of sporadic PD is still unknown; however, there is general consensus that the accumulation and aggregation of α-synuclein (α-syn) are among the prominent pathological features. The precise function of α-syn in the healthy human brain is not agreed upon, although it has been reported to play a role in vesicular trafficking and neurotransmitter release. Dutch Juvenile-1 (DJ-1) is a multifunctional protein involved in regulating an array of mechanisms, including oxidative stress, ferroptosis, mitochondrial and dopamine homeostasis. Loss-of-function of DJ-1 was reported to cause familial PD, and oxidative inactivation of DJ-1 has been observed in sporadic cases, suggesting that both genetic and post-translational events converge on common disease pathways. This review proposes that loss of DJ-1 function may elevate intracellular α-syn levels, leading to their aggregation and consequent neurotoxicity. Reports suggest that DJ-1 can inhibit α-syn aggregation, facilitate α-syn clearance via chaperone-mediated autophagy, and act as a deglycase or glyoxalase to neutralize glycated α-syn species. Clinical studies have also reported altered DJ-1 oxidation states in PD patient samples, supporting its potential as a biomarker. By bridging familial and sporadic PD mechanisms, DJ-1 emerges as a compelling therapeutic target with the potential to mitigate α-syn–mediated neurodegeneration across both forms. However, further research is required to fully establish its clinical relevance and translational potential. Full article

Hyperglycemia in early-stage embryogenesis is linked to diabetic embryopathy. High-glucose-concentration-induced accumulation of hexokinase-2 (HK2) may initiate metabolic dysfunction that contributes to diabetic embryopathy, including increased formation of methylglyoxal (MG). In this study, we evaluated changes in HK2 protein levels and embryo dysmorphogenesis in an experimental model of diabetic embryopathy. Rat embryos were cultured with high glucose concentrations, and the effects of glyoxalase 1 (Glo1) inducer, trans-resveratrol and hesperetin (tRES + HESP) were evaluated. Rat embryos, on gestational day 9, were cultured for 48 h in low and high glucose concentrations with or without tRES + HESP. Embryo crown–rump length, somite number, malformation score, concentrations of HK2 and Glo1 protein, rates of glucose consumption, and MG formation were assessed. Under low-glucose conditions, embryos exhibited normal morphogenesis. In contrast, high-glucose conditions led to reduced crown–rump length and somite number, and an increased malformation score. The addition of 10 μM tRES + HESP reversed these high glucose-induced changes by 60%, 49%, and 47%, respectively. Embryos cultured in high glucose showed increases in HK2 concentration (42%), glucose consumption (75%), and MG formation (27%), normalized to embryo volume. These elevated HK2 levels were normalized by treatment with 10 μM tRES + HESP. Thus, high-glucose-induced metabolic dysfunction and embryopathy may both be initiated by HK2 accumulation and may be preventable with tRES + HESP treatment. Full article