Oxidative Stress in Healthy and Pathological Red Blood Cells

Biomolecules, Journal Year: 2023, Volume and Issue: 13(8), P. 1262 - 1262

Published: Aug. 18, 2023

Red cell diseases encompass a group of inherited or acquired erythrocyte disorders that affect the structure, function, production red blood cells (RBCs). These can lead to various clinical manifestations, including anemia, hemolysis, inflammation, and impaired oxygen-carrying capacity. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) antioxidant defense mechanisms, plays significant role in pathophysiology diseases. In this review, we discuss most relevant oxidant involved RBC damage, enzymatic low molecular weight systems protect RBCs against oxidative injury, finally, stress different diseases, sickle disease, glucose 6-phosphate dehydrogenase deficiency, pyruvate kinase highlighting underlying mechanisms leading pathological phenotypes.

Language: Английский

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Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 647 - 647

Published: Feb. 2, 2024

Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced death, known as cuproptosis, its disease implications, including cancer therapy. Copper ionophores, such elesclomol disulfiram, increase intracellular copper levels. elevation triggers oxidative stress subsequent offering implications in Additionally, ionophores disrupt mitochondrial respiration protein lipoylation, further contributing toxicity death. Potential targets biomarkers are identified, can be targeted those proteins trigger cuproptosis. The role different cancers is discussed understand therapies using nanomaterials, chelators. Furthermore, explored through diseases Wilson Menkes physiological copper. Exploring cuproptosis presents opportunity improve treatments copper-related disorders cancers, with bring significant advancements modern medicine.

Language: Английский

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Unraveling the AMPK-SIRT1-FOXO Pathway: The In-Depth Analysis and Breakthrough Prospects of Oxidative Stress-Induced Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 70 - 70

Published: Jan. 9, 2025

Oxidative stress (OS) refers to the production of a substantial amount reactive oxygen species (ROS), leading cellular and organ damage. This imbalance between oxidant antioxidant activity contributes various diseases, including cancer, cardiovascular disease, diabetes, neurodegenerative conditions. The body’s system, mediated by signaling pathways, includes AMPK-SIRT1-FOXO pathway. In oxidative conditions, AMPK, an energy sensor, activates SIRT1, which in turn stimulates FOXO transcription factor. cascade enhances mitochondrial function, reduces damage, mitigates OS-induced injury. review provides comprehensive analysis biological roles, regulatory mechanisms, functions pathway diseases influenced OS, offering new insights methods for understanding OS pathogenesis its therapeutic approaches.

Language: Английский

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Plant Glutathione Peroxidases: Non-Heme Peroxidases with Large Functional Flexibility as a Core Component of ROS-Processing Mechanisms and Signalling

Antioxidants, Journal Year: 2022, Volume and Issue: 11(8), P. 1624 - 1624

Published: Aug. 21, 2022

Glutathione peroxidases (GPXs) are non-heme catalyzing the reduction of H2O2 or organic hydroperoxides to water corresponding alcohols using glutathione (GSH) thioredoxin (TRX) as a reducing agent. In contrast animal GPXs, plant enzymes non-seleno monomeric proteins that generally utilize TRX more effectively than GSH but can be putative link between two main redox systems. Because substantial differences compared non-plant use GPX-like (GPXL) name was suggested for Arabidopsis enzymes. GPX(L)s not only protect cells from stress-induced oxidative damages crucial components development and growth. Due fine-tuning metabolism homeostasis, they involved in whole life cycle even under normal growth conditions. Significantly new mechanisms were discovered related their transcriptional, post-transcriptional post-translational modifications by describing gene regulatory networks, interacting microRNA families, identifying Lys decrotonylation enzyme activation. Their involvement epigenetic evidenced. Detailed genetic, evolutionary, bio-chemical characterization, comparison functions demonstrated species-specific roles. The multisided regulation entire ensure significance will widely recognized applied future.

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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Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 291 - 291

Published: Feb. 27, 2024

The amino acid transporters SLC38A5 and SLC7A11 are upregulated in triple-negative breast cancer (TNBC). transports glutamine, methionine, glycine serine, therefore activates mTOR signaling induces epigenetic modifications. cystine increases the cellular levels of glutathione, which protects against oxidative stress lipid peroxidation via glutathione peroxidase, a seleno (Se)-enzyme. primary source Se is dietary Se-methionine (Se-Met). Since we examined its role Se-Met uptake TNBC cells. We found that interacts with methionine comparable affinity. also influence on Nrf2 activated induced expression Nrf2-target genes, including SLC7A11. Our previous work discovered niclosamide, an antiparasitic drug, as potent inhibitor SLC38A5. Here, to be inhibited by niclosamide IC50 value range 0.1–0.2 μM. In addition direct inhibition SLC7A11, pretreatment cells reduced both transporters. Niclosamide decreased levels, proliferation, suppressed GPX4 expression, increased peroxidation, ferroptosis It significantly growth cell line MB231 mouse xenografts.

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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Therapeutic Approaches with Iron Oxide Nanoparticles to Induce Ferroptosis and Overcome Radioresistance in Cancers

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 325 - 325

Published: Feb. 26, 2025

The emergence of nanotechnology in medicine, particularly using iron oxide nanoparticles (IONPs), may impact cancer treatment strategies. IONPs exhibit unique properties, such as superparamagnetism, biocompatibility, and ease surface modification, making them ideal candidates for imaging, therapeutic interventions. Their application targeted drug delivery, especially with traditional chemotherapeutic agents like cisplatin, has shown potential overcoming limitations low bioavailability systemic toxicity chemotherapies. Moreover, IONPs, by releasing ions, can induce ferroptosis, a form iron-dependent cell death, which offers promising pathway to reverse radio- chemoresistance therapy. In particular, demonstrate significant radiosensitisers, enhancing the effects radiotherapy promoting reactive oxygen species (ROS) generation, lipid peroxidation, modulating tumour microenvironment stimulate antitumour immune responses. This review explores multifunctional roles radiosensitisation through ferroptosis induction, highlighting their promise advancing head neck cancers. Additional research is crucial fully addressing clinical settings, offering novel approach personalised treatment.

Language: Английский

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Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3829 - 3829

Published: Nov. 29, 2022

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD associated iron accumulation and suggested to be driven part by novel cell death pathway, ferroptosis. A unique modality death, ferroptosis mediated iron-dependent phospholipid peroxidation. mechanisms inhibitors enhance antioxidative capacity counter oxidative stress from lipid peroxidation, such as through system xc−/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis coenzyme Q10 (CoQ10)/FSP1 pathway. Another means reduce chelators. To date, there no disease-modifying therapy cure or slow progression, a recent topic research seeks intervene development via regulation In this review, we provide discussion different pathways, molecular ferroptosis, role blood–brain barrier damage, updates on studies latest progress pharmacological agents targeting for intervention clinical trials.

Language: Английский

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Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1581 - 1581

Published: Oct. 28, 2022

A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se metabolized and incorporated as amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) thioredoxin reductases (TXNRDs), among others. Both processes Sec metabolism for production selenoproteins action are utilized by cells from solid tumors a protective mechanism against oxidative damage to resist ferroptosis, an iron-dependent cell death mechanism. Protection ferroptosis requires sustained selenoprotein GPX4, which involves increasing uptake Se, potentially activating metabolic pathways such trans-selenation pathway TXNRD1-dependent decomposition inorganic selenocompounds sustain GPX4 synthesis. Additionally, endoplasmic reticulum-resident also affect apoptotic responses presence selenocompounds. Selenoproteins may help adapting increased challenges modified nutrient that result Warburg switch. Finally, rewire hierarchy use Se-related machinery prioritize essential adaptations damage. In this review, we discuss both evidence gaps knowledge on how Sec, promote their survival particularly via resistance ferroptosis.

Language: Английский

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