Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(5), P. 1323 - 1367

Published: March 14, 2024

Abstract Reactive oxygen species (ROS) and reactive nitrogen (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production elimination is termed oxidative stress, critical factor common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic neurological disorders (Alzheimer’s Parkinson’s diseases), other disorders. To counteract the harmful effects ROS, organisms have evolved complex, three-line antioxidant defense system. The first-line mechanism most efficient involves enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). This line plays an irreplaceable role in dismutation radicals (O 2 ·− ) hydrogen peroxide (H O ). removal by SOD prevents formation much more damaging peroxynitrite ONOO − + NO · → maintains physiologically relevant level nitric oxide (NO ), important molecule neurotransmission, inflammation, vasodilation. second-line pathway exogenous diet-derived small-molecule antioxidants. third-line ensured repair oxidized proteins biomolecules variety enzyme review briefly discusses endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) (e.g., smoking, radiation, drugs, pollution) sources (superoxide radical, peroxide, hydroxyl peroxyl hypochlorous acid, peroxynitrite). Attention has been given system provided SOD, CAT, GPx. chemical molecular mechanisms enzymes, enzyme-related (cancer, cardiovascular, lung, metabolic, GPx4) cellular processes ferroptosis discussed. Potential therapeutic applications mimics recent progress metal-based (copper, iron, cobalt, molybdenum, cerium) nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) also Moreover, attention action low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids β-carotene, lycopene, lutein), flavonoids quercetin, anthocyanins, epicatechin), (GSH)), activation transcription factors Nrf2, protection against diseases. Given that there discrepancy preclinical clinical studies, approaches may result greater pharmacological success therapies subject discussion.

Language: Английский

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Research progress of glutathione peroxidase family (GPX) in redoxidation

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 2, 2023

Maintaining the balance of a cell’s redox function is key to determining cell fate. In critical system mammalian cells, glutathione peroxidase (GPX) most prominent family proteins with multifaceted that affects almost all cellular processes. A total eight members GPX are currently found, namely GPX1-GPX8. They have long been used as antioxidant enzymes play an important role in combating oxidative stress and maintaining balance. However, each member has different mechanism action site GPX1-4 GPX6 use selenocysteine active center catalyze reduction H 2 O or organic hydroperoxides water corresponding alcohols, thereby reducing their toxicity addition small molecule hydroperoxides, GPX4 also capable complex lipid compounds. It only enzyme directly reduces destroys hydroperoxides. The sites GPX5 GPX7-GPX8 do not contain selenium cysteine (Secys), but instead, residues (Cys) sites. mainly expressed epididymal tissue plays protecting sperm from stress. Both enzymes, GPX7 GPX8, located endoplasmic reticulum necessary involved folding proteins, GPX8 regulation Ca 2+ reticulum. With in-depth understanding health disease development, become functional core family, order further clarify expression regulatory process, we reviewed separately.

Language: Английский

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Cellular Red-Ox system in health and disease: The latest update

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114606 - 114606

Published: March 28, 2023

Cells are continually exposed to reactive oxygen species (ROS) generated during cellular metabolism. Apoptosis, necrosis, and autophagy biological processes involving a feedback cycle that causes ROS molecules induce oxidative stress. To adapt exposure, living cells develop various defense mechanisms neutralize use as signaling molecule. The redox networks combine pathways regulate cell metabolism, energy, survival, death. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) essential antioxidant enzymes required for scavenging in compartments response stressful situations. Among the non-enzymatic defenses, vitamin C, (GSH), polyphenols, carotenoids, E, etc., also essential. This review article describes how produced byproducts of oxidation/reduction (redox) antioxidants system is directly or indirectly engaged ROS. In addition, we used computational methods determine comparative profile binding energies several with enzymes. analysis demonstrates high affinity their structures.

Language: Английский

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Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102066 - 102066

Published: Sept. 7, 2023

Language: Английский

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Natural dietary ROS scavenger-based nanomaterials for ROS-related chronic disease prevention and treatment

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 490, P. 151756 - 151756

Published: April 30, 2024

Language: Английский

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Selenium and Selenoproteins: Mechanisms, Health Functions, and Emerging Applications

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 437 - 437

Published: Jan. 21, 2025

Selenium (Se) is an essential trace element crucial for human health that primarily functions as immunonutrient. It incorporated into polypeptides such selenocysteine (SeC) and selenomethionine (SeMet), two key amino acids involved in various biochemical processes. All living organisms can convert inorganic Se biologically active organic forms, with SeMet being the predominant form a precursor SeC production humans animals. The genome encodes 25 selenoprotein genes, which incorporate low-molecular-weight compounds of SeC. Organic Se, especially selenoproteins, more efficiently absorbed than driving demand selenoprotein-based products, functional foods. Se-enriched foods offer practical means delivering bioavailable are associated enhanced antioxidant properties benefits. Recent advancements synthesis have improved our understanding their roles defense, cancer prevention, immune regulation, anti-inflammation, hypoglycemia, cardiovascular health, Alzheimer’s disease, fertility, COVID-19. This review highlights selenoproteins biological functions, biosynthetic pathways, emerging applications while highlighting need further research.

Language: Английский

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Side-by-side comparison of recombinant human glutathione peroxidases identifies overlapping substrate specificities for soluble hydroperoxides

Redox Biology, Journal Year: 2023, Volume and Issue: 59, P. 102593 - 102593

Published: Jan. 2, 2023

Five out of eight human glutathione peroxidases (GPXs) are selenoproteins, representing proteins that contain selenium as part the amino acid selenocysteine. The GPXs important for reducing hydroperoxides in a glutathione-consuming manner and thus regulate cellular redox homeostasis. GPX1, GPX2, GPX4 represent three main cytosolic GPXs, but they differ their expression patterns with GPX1 being expressed ubiquitously, whereas GPX2 is mainly epithelial cells. have been described to reduce soluble hydroperoxides, while reduces complex lipid protecting cells from peroxidation ferroptosis. But most these data derived devoid one isoforms thus, compensation or other effects might affect conclusions. So far, use isolated recombinant selenoprotein pure enzyme assays has not employed study substrate specificities side by side. Using produced E. coli we here assessed GPX activities NADPH-consuming reductase-coupled assay 17 different peroxides (all at 50 μM) substrates. was clearly only isoform able phosphatidylcholine hydroperoxide. In contrast, small such H2O2, cumene hydroperoxide, tert-butyl hydroperoxide were reduced all isoforms, approximately 10-fold higher efficiency comparison GPX4. Also, several fatty acid-derived again had highest activity. Interestingly, stereoisomerism affected activity enzymes. Overall, distinct specificity obvious GPX4, so when comparing GPX2. Clearly potent terms turnover reduction fatty-acid hydroperoxides.

Language: Английский

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Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1341 - 1341

Published: May 8, 2023

Reactive oxygen species (ROS) are radical intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds buffering capacity antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC shifts vascular system into a pro-coagulative, proinflammatory state, thereby increasing risk developing cardiovascular (CV) diseases metabolic disorders. Studies have turned to investigation microRNA treatment for CV factors, post-transcription regulators known co-regulate ROS. In this review, we will discuss ROS pathways generation, normal physiology ROS-induced dysfunction, current knowledge common disorders their connection stress. Therapeutic strategies based on microRNAs response microRNA’s regulatory roles controlling also be explored. It is gain an in-depth comprehension mechanisms generating how manipulating enzymatic byproducts can protect function from prevent development

Language: Английский

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Selenium—More than Just a Fortuitous Sulfur Substitute in Redox Biology

Molecules, Journal Year: 2023, Volume and Issue: 29(1), P. 120 - 120

Published: Dec. 24, 2023

Living organisms use selenium mainly in the form of selenocysteine active site oxidoreductases. Here, selenium’s unique chemistry is believed to modulate reaction mechanism and enhance catalytic efficiency specific enzymes ways not achievable with a sulfur-containing cysteine. However, despite fact that selenium/sulfur have different physicochemical properties, several selenoproteins fully functional cysteine-containing homologues some do at all. In this review, selected selenocysteine-containing proteins will be discussed showcase both situations: (i) as an obligatory element for protein’s physiological function, (ii) presenting no clear advantage over sulfur (functional either or sulfur). Selenium’s roles antioxidant defence (to maintain cellular redox status/hinder oxidative stress), hormone metabolism, DNA synthesis, repair (maintain genetic stability) also highlighted, well role human health. Formate dehydrogenases, hydrogenases, glutathione peroxidases, thioredoxin reductases, iodothyronine deiodinases herein featured.

Language: Английский

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The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1928 - 1928

Published: Oct. 29, 2023

Chronic liver disease (CLD) affects a significant portion of the global population, leading to substantial number deaths each year. Distinct forms like non-alcoholic fatty (NAFLD) and alcoholic (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central metabolism, mitochondria are essential for ATP production, gluconeogenesis, acid oxidation, heme synthesis. However, diseases NAFLD, ALD, fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, metabolic irregularities. This dysfunction, especially electron leakage, exacerbates production reactive oxygen species (ROS), augmenting damage. Amidst this, nuclear factor erythroid 2-related 2 (NRF2) emerges as cellular protector. It not only counters stress regulating antioxidant genes but also maintains health overseeing autophagy biogenesis. The synergy between NRF2 modulation introduces new therapeutic potentials CLD, focusing on preserving integrity against threats. review delves into intricate role shedding light innovative strategies its prevention treatment, through pathways.

Language: Английский

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