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

Archives of Toxicology, Год журнала: 2024, Номер 98(5), С. 1323 - 1367

Опубликована: Март 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.

Язык: Английский

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GPX4 in cell death, autophagy, and disease

Autophagy, Год журнала: 2023, Номер 19(10), С. 2621 - 2638

Опубликована: Июнь 4, 2023

Selenoprotein GPX4 (glutathione peroxidase 4), originally known as PHGPX (phospholipid hydroperoxide glutathione peroxidase), is the main oxidoreductase in use of a reducing agent scavenging lipid peroxidation products. There are three isoforms: cytosolic (cGPX4), mitochondrial (mGPX4), and nuclear (nGPX4), with distinct spatiotemporal expression patterns during embryonic development adult life. In addition to inducing phenotype ferroptosis, loss can some cells trigger apoptosis, necroptosis, pyroptosis, or parthanatos, which mediates accelerates developmental defects, tissue damage, sterile inflammation. The interaction autophagic degradation pathway further modulates cell fate response oxidative stress. Impaired function implicated tumorigenesis, neurodegeneration, infertility, inflammation, immune disorders, ischemia-reperfusion injury. Additionally, R152H mutation promote Sedaghatian-type spinal metaphyseal dysplasia, rare fatal disease newborns. Here, we discuss roles classical functions well emerging GPX4-regulated processes death, autophagy, disease.Abbreviations: AA: arachidonic acid; cGPX4: GPX4; CMA: chaperone-mediated autophagy; DAMPs: danger/damage-associated molecular patterns; mGPX4: nGPX4: GSDMD-N: N-terminal fragment GSDMD; I/R: ischemia-reperfusion; PLOOH: phospholipid hydroperoxide; PUFAs: polyunsaturated fatty acids; RCD: regulated death; ROS: reactive oxygen species; Se: selenium; SSMD: spondylometaphyseal dysplasia; UPS: ubiquitin-proteasome system

Язык: Английский

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GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116512 - 116512

Опубликована: Апрель 3, 2024

GPX4 (Glutathione peroxidase 4) serves as a crucial intracellular regulatory factor, participating in various physiological processes and playing significant role maintaining the redox homeostasis within body. Ferroptosis, form of iron-dependent non-apoptotic cell death, has gained considerable attention recent years due to its involvement multiple pathological processes. is closely associated with ferroptosis functions primary inhibitor this process. Together, contribute pathophysiology several diseases, including sepsis, nervous system ischemia reperfusion injury, cardiovascular cancer. This review comprehensively explores roles impacts development progression these aim providing insights for identifying potential therapeutic strategies future.

Язык: Английский

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Oxidative Stress in Healthy and Pathological Red Blood Cells

Biomolecules, Год журнала: 2023, Номер 13(8), С. 1262 - 1262

Опубликована: Авг. 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.

Язык: Английский

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Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience

Cancer Letters, Год журнала: 2023, Номер 559, С. 216119 - 216119

Опубликована: Март 7, 2023

Язык: Английский

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Ferroptosis in immunostimulation and immunosuppression

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 199 - 210

Опубликована: Июль 9, 2023

Summary Ferroptosis is a form of iron‐dependent regulated cell death characterized by the accumulation toxic lipid peroxides, particularly in plasma membrane, leading to lytic death. While it plays crucial role maintaining overall health and proper functioning multicellular organisms, can also contribute tissue damage pathological conditions. Although ferroptotic generally recognized as an immunostimulatory process associated with release damage‐associated molecular patterns (DAMPs), occurrence ferroptosis immune cells or immunosuppressive molecules result tolerance. Consequently, there ongoing exploration targeting upstream signals machinery therapeutically enhance inhibit response. In addition introducing core mechanisms ferroptosis, we will focus on characteristics conditions, context infection, sterile inflammation, tumor immunity.

Язык: Английский

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Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond

Protein & Cell, Год журнала: 2024, Номер 15(9), С. 642 - 660

Опубликована: Фев. 29, 2024

Abstract Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell as unique forms regulated resulting from an imbalance in the cellular metabolism. This review discusses mechanisms death—ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis—and explores their potential cancer therapy. Our underscores complexity pathways offers insights into innovative therapeutic avenues for treatment.

Язык: Английский

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

Cancers, Год журнала: 2024, Номер 16(3), С. 647 - 647

Опубликована: Фев. 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.

Язык: Английский

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In defence of ferroptosis

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Язык: Английский

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PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Язык: Английский

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