Enhancing Salt Tolerance in Soybean by Exogenous Boron: Intrinsic Study of the Ascorbate-Glutathione and Glyoxalase Pathways

Boron (B) performs physiological functions in higher plants as an essential micronutrient, but its protective role in salt stress is poorly understood. Soybean (Glycine max L.) is planted widely throughout the world, and salinity has adverse effects on its physiology. Here, the role of B (1 mM boric acid) in salt stress was studied by subjecting soybean plants to two levels of salt stress: mild (75 mM NaCl) and severe (150 mM NaCl). Exogenous B relieved oxidative stress by enhancing antioxidant defense system components, such as ascorbate (AsA) levels, AsA/dehydroascorbate ratios, glutathione (GSH) levels, the GSH and glutathione disulfide ratios, and ascorbate peroxidase, monodehydroascorbate reductase, and dehydroascorbate reductase activities. B also enhanced the methylglyoxal detoxification process by upregulation of the components of the glyoxalase system in salt-stressed plants. Overall, B supplementation enhanced antioxidant defense and glyoxalase system components to alleviate oxidative stress and MG toxicity induced by salt stress. B also improved the physiology of salt-affected soybean plants.

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.

Maize Grain Extract Enriched with Polyamines Alleviates Drought Stress in Triticum aestivum through Up-Regulation of the Ascorbate-Glutathione Cycle, Glyoxalase System, and Polyamine Gene Expression

The potential protective role of priming wheat seeds with maize green extract (MGE) against the stress effects of drought was studied. Pretreatment using MGE, MGE enriched with polyamines (MGEPA), and drought treatments (irrigation deficit of 30% (severe drought) or 60% (moderate drought) versus 90% relative water content of soil as a control) were applied in a factorial completely randomized design. Under moderate drought, pretreatment with MGEPA outperformed MGE and control, while severely stressed plants died even with pretreatments. Both extracts enhanced normal plant growth and yield and mitigated the deleterious effect of moderately stressed plants. Application of both extracts markedly increased photosynthetic efficiency, membrane stability, relative water content, and accumulation of antioxidants, osmoprotectants, trans- and cis-zeatin, polyamines, and their gene expressions, while levels of superoxide (O2•‒) and hydrogen peroxide (H2O2), lipid peroxidation, and electrolyte leakage were decreased. Enzymatic antioxidants and glyoxalase system activities were improved in moderately stressed plants and were further improved with pretreatment with both extracts, thus protecting plants from oxidative damage by up-regulation of the ascorbate–glutathione cycle. Glycine betaine, soluble sugars, and proline levels were greatly increased in pretreated plants, thus maintaining membrane stability and photosynthetic efficiency. The interaction between drought and pretreatment using MGEPA was significant in growing wheat plants in dry environments with 60% relative water content of soil.

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.

Biochemical Regulation of the Glyoxalase System in Response to Insulin Signaling

Methylglyoxal (MG) is a reactive glycation metabolite and potentially induces dicarbonyl stress. The production of MG in cells is increased along with an increase in carbohydrate metabolism. The efficiency of the glyoxalase system, consisting of glyoxalase 1 (GlxI) and glyoxalase 2 (GlxII), is crucial for turning the accumulated MG into nontoxic metabolites. Converting MG-glutathione hemithioacetal to S-d-lactoylglutathione by GlxI is the rate-determining step of the enzyme system. In this study, we found lactic acid accumulated during insulin stimulation in cells, however, cellular MG and S-d-lactoylglutathione also increased due to the massive flux of glycolytic intermediates. The insulin-induced accumulation of MG and S-d-lactoylglutathione were efficiently removed by the treatment of metformin, possibly via affecting the glyoxalase system. With the application of isotopic 13C3-MG, the flux of MG from extracellular and intracellular origins was dissected. While insulin induced an influx of extracellular MG, metformin inhibited the trafficking of MG across the plasma membrane. Therefore, metformin could maintain the extracellular MG by means of reducing the secretion of MG rather than facilitating the scavenging. In addition, metformin may affect the glyoxalase system by controlling the cellular redox state through replenishing reduced glutathione. Overall, alternative biochemical regulation of the glyoxalase system mediated by insulin signaling or molecules like biguanides may control cellular MG homeostasis.