• BMB Reports
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• v.43 no.9
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• pp.584-592
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• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.

• Molecules and Cells
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• v.28 no.5
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• pp.479-487
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• 2009

Glutathione reductase (GR) is an enzyme that recycles a key cellular antioxidant molecule glutathione (GSH) from its oxidized form (GSSG) thus maintaining cellular redox homeostasis. A recombinant plasmid to overexpress a GR of Brassica rapa subsp. pekinensis (BrGR) in E. coli BL21 (DE3) was constructed using an expression vector pKM260. Expression of the introduced gene was confirmed by semi-quantitative RT-PCR, immunoblotting and enzyme assays. Purification of the BrGR protein was performed by IMAC method and indicated that the BrGR was a dimmer. The BrGR required NADPH as a cofactor and specific activity was approximately 458 U. The BrGR-expressing E. coli cells showed increased GR activity and tolerance to $H_2O_2$, menadione, and heavy metal ($CdCl_2$, $ZnCl_2$ and $AlCl_2$)-mediated growth inhibition. The ectopic expression of BrGR provoked the co-regulation of a variety of antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase. Consequently, the transformed cells showed decreased hydroperoxide levels when exposed to stressful conditions. A proteomic analysis demonstrated the higher level of induction of proteins involved in glycolysis, detoxification/oxidative stress response, protein folding, transport/binding proteins, cell envelope/porins, and protein translation and modification when exposed to $H_2O_2$ stress. Taken together, these results indicate that the plant GR protein is functional in a cooperative way in the E. coli system to protect cells against oxidative stress.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.553-560
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• 2005

The purpose of this study was to examine the lipid peroxidation, plasma antioxidant status and insulin resistance in childhood obesity. To this end, we measured blood lipid profiles, glucose, insulin concentrations, plasma antioxidant vitamins, baseline conjugated diene formation as a measure of LDL oxidation in vivo and TRAP (total radical trapping antioxidant potential) of 93 school children (58 nonobese, 35 overweight-obese). Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). The overweight-obese children showed significantly higher levels of leptin (p < 0.0001) and triglyceride (p < 0.05) and significantly lower level of plasma Iycopene (p < 0.001) and $\gamma$-tocopherol (p < 0.05) compared with the normal weight children. Furthermore, the levels of TRAP were significantly lower in overweight-obese children (p < 0.05). Significant positive relationships between plasma leptin and conjugated dienes formation (p < 0.005) and inverse relationship between plasma leptin and lipid corrected levels of $\beta$-carotene (p < 0.05), Iycopene (p < 0.05) were observed. Our results showed an increased lipid peroxidation and decreased antioxidant capacity in childhood obesity which could be involved in the atherosclerotic process.

• Molecules and Cells
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• v.46 no.3
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• pp.165-175
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• 2023

The transcription factor Nrf2 was originally identified as a master regulator of redox homeostasis, as it governs the expression of a battery of genes involved in mitigating oxidative and electrophilic stress. However, the central role of Nrf2 in dictating multiple facets of the cellular stress response has defined the Nrf2 pathway as a general mediator of cell survival. Recent studies have indicated that Nrf2 regulates the expression of genes controlling ferroptosis, an iron-and lipid peroxidation-dependent form of cell death. While Nrf2 was initially thought to have anti-ferroptotic function primarily through regulation of the antioxidant response, accumulating evidence has indicated that Nrf2 also exerts anti-ferroptotic effects via regulation of key aspects of iron and lipid metabolism. In this review, we will explore the emerging role of Nrf2 in mediating iron homeostasis and lipid peroxidation, where several Nrf2 target genes have been identified that encode critical proteins involved in these pathways. A better understanding of the mechanistic relationship between Nrf2 and ferroptosis, including how genetic and/or pharmacological manipulation of Nrf2 affect the ferroptotic response, should facilitate the development of new therapies that can be used to treat ferroptosis-associated diseases.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.5
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• pp.443-454
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• 2021

Purpose: Due to the increasing prevalence of obesity worldwide, non-alcoholic fatty liver disease (NAFLD) has reached epidemic dimensions over time. NAFLD is the most common cause of childhood chronic liver disease. There is a relationship between NAFLD and oxidative stress. This study aims to investigate the changes in thiol/disulfide homeostasis parameters to determine the oxidant/antioxidant balance in obese rats with diet-induced NAFLD and healthy rats. Methods: Twelve Wistar albino rats were used in this study. Experimentally produced NAFLD obese rats (n=6) and healthy rats were compared. Experimental NAFLD model was created with a special fatty liver diet (Altromin^® C1063, Fatty Liver Diet, Exclusivet, Lage, Germany). The biochemical and histopathological features of the groups, as well as serum thiol/disulfide homeostasis parameters, were analyzed and compared. Results: In the experimentally induced NAFLD rat model, they gained more weight than the control group. Steatosis (at least grade 2) occurred in all rats fed with special fatty liver diet for 12 weeks. Histopathologically, no high-grade inflammation was observed in rats with experimental NAFLD after feeding a diet for 12 weeks. Results revealed that aspartate transaminase and alanine transaminase levels were high, albumin levels were low, oxidant stress parameters increased, and antioxidant thiol groups decreased. Conclusion: Experimental NAFLD is characterized by increased oxidant stress accompanying fatty tissue in the liver. Analysis of thiol/disulfide homeostasis parameters in NAFLD can be used in further studies to develop effective treatment options.

• The Plant Pathology Journal
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• v.40 no.3
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• pp.235-250
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• 2024

During the infection process, plant pathogenic fungi encounter plant-derived oxidative stress, and an appropriate response to this stress is crucial to their survival and establishment of the disease. Plant pathogenic fungi have evolved several mechanisms to eliminate oxidants from the external environment and maintain cellular redox homeostasis. When oxidative stress is perceived, various signaling transduction pathways are triggered and activate the downstream genes responsible for the oxidative stress response. Despite extensive research on antioxidant systems and their regulatory mechanisms in plant pathogenic fungi, the specific functions of individual antioxidants and their impacts on pathogenicity have not recently been systematically summarized. Therefore, our objective is to consolidate previous research on the antioxidant systems of plant pathogenic fungi. In this review, we explore the plant immune responses during fungal infection, with a focus on the generation and function of reactive oxygen species. Furthermore, we delve into the three antioxidant systems, summarizing their functions and regulatory mechanisms involved in oxidative stress response. This comprehensive review provides an integrated overview of the antioxidant mechanisms within plant pathogenic fungi, revealing how the oxidative stress response contributes to their pathogenicity.

• ALGAE
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• v.25 no.4
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• pp.155-171
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• 2010

The underlying physiology of algal antioxidant compounds is reviewed in the context of seaweed biology and utilization. The application of seaweed antioxidants in foods, food supplements, nutraceuticals and medicine is considered from the perspective of benefits to human health. We advocate that direct consumption of seaweed products for their antioxidant composition alone provides a useful alternative to non-natural substances, while simultaneously providing worthwhile nutritional benefits. Economic utilization of seaweeds for their antioxidant properties remains in its infancy. This review provides examples ranging from laboratory studies through to clinical trials where antioxidants derived from seaweeds may provide major health benefits that warrant subsequent investigative studies and possible utilization.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.5
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• pp.588-597
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• 2010

We investigated the effect of quercetin on growth and plasma cholesterol level and the effects of quercetin pretreatment (Diet 1, 0%; Diet 2, 0.25%; and Diet 3, 0.5% quercetin) for 30 and 60 days on oxidative stress induced by hypo-osmotic conditions (17.5, 8.75, and 4 psu) in olive flounder. The weights of flounder were higher with Diet 3 than with Diet 1 and 2, which indicated that a high concentration (Diet 3) of quercetin was very effective in growth. Total cholesterol levels were lower with Diets 2 and 3 than with Diet 1, leading us to hypothesize that quercetin removed low-density lipoproteins from circulation and thereby reduced total cholesterol. To understand the antioxidant role of quercetin, we measured the mRNA expression and activities of superoxide dismutase (SOD) and catalase (CAT) and the $H_2O_2$ concentration in quercetin-treated flounder exposed to osmotic stress. The $H_2O_2$ concentration and the SOD and CAT expression and activity levels were lower in flounder fed with Diets 2 and 3 than with Diet 1, suggesting that quercetin directly scavenges reactive oxygen species to reduce oxidative stress. Furthermore, the plasma lysozyme activity and osmolality were higher with Diets 2 and 3 than with Diet 1, indicating that quercetin increases immune function and helps to maintain physiological homeostasis. Plasma cortisol was lower with Diets 2 and 3 than with Diet 1, suggesting the quercetin protects against stress. These results indicate that quercetin has hypocholesterolemic and antioxidant effects, increases immune function, and acts to maintain physiological homeostasis.

• Korean Journal of Soil Science and Fertilizer
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• v.51 no.2
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• pp.90-100
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• 2018

Environmental pollution with arsenic (As) in croplands causes agricultural and health problems worldwide. Rice is an important crop in South Korea, and many studies have evaluated the relationship between As and glutathione (GSH) to alleviate As uptake from the soil into plants. However, information about the relationship between As and ascorbate (AsA) in rice seedlings is still limited with regard to As phytotoxicity. We therefore investigated changes in reactive oxygen species (ROS) and antioxidant levels in rice (Oryza sativa L. cv 'Dasan') seedlings with toxic As and/or AsA application. The exposure of rice seedlings to $15{\mu}M$ As inhibited plant growth and resulted in increased contents of superoxide, hydrogen peroxide, and malondialdehyde, and induced As uptake by the roots and leaves. Application of AsA to As-exposed seedlings ameliorated As-induced oxidative stress by enhancing the capacity of AsA-GSH cycle in applied plants and increasing As transfer from the roots to leaves. These results suggest that AsA application alleviated As-induced oxidative damage by maintaining sufficient levels of AsA and GSH.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.519-528
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• 2019

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by $H_2O_2$ was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.