GPX4, ferroptosis, and diseases

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116512 - 116512

Published: April 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.

Language: Английский

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Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114312 - 114312

Published: May 19, 2023

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its pathogenesis limitations clinical treatment strategies, it poses serious medical challenge burden worldwide. The AD not clear, potential biological mechanisms include aggregation soluble amyloid form insoluble plaques, abnormal phosphorylation tau protein formation intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress metal ion disorders. Among them, ferroptosis newly discovered programmed cell death induced iron-dependent lipid peroxidation reactive oxygen species. Recent studies have shown that closely related AD, but the mechanism remains unclear. may be iron metabolism, amino acid metabolism affecting accumulation ions. Some chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine derivatives, antioxidants (vitamin E, lipoic acid, selenium), derivatives Fer-1, tet, etc. been in animal effective exert neuroprotective effects. This review summarizes regulation natural plant products on order provide reference information for future research development inhibitors.

Language: Английский

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The mechanisms of ferroptosis and its role in atherosclerosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112

Published: Jan. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Language: Английский

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A chemo/chemodynamic nanoparticle based on hyaluronic acid induces ferroptosis and apoptosis for triple-negative breast cancer therapy

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 329, P. 121795 - 121795

Published: Jan. 9, 2024

Language: Английский

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Ferroptosis: Promising approach for cancer and cancer immunotherapy

Cancer Letters, Journal Year: 2023, Volume and Issue: 561, P. 216152 - 216152

Published: April 4, 2023

Language: Английский

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Polyunsaturated fatty acids-induced ferroptosis suppresses pancreatic cancer growth

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 22, 2024

Abstract Despite recent advances in science and medical technology, pancreatic cancer remains associated with high mortality rates due to aggressive growth no early clinical sign as well the unique resistance anti-cancer chemotherapy. Current numerous investigations have suggested that ferroptosis, which is a programed cell death driven by lipid oxidation, an attractive therapeutic different tumor types including cancer. Here, we first demonstrated linoleic acid (LA) α-linolenic (αLA) induced necroptotic morphological change MIA-Paca2 Suit 2 lines. LA αLA increased peroxidation phosphorylation of RIP3 MLKL cancers, were negated ferroptosis inhibitor, ferrostatin-1, restoring back BSA control levels. Similarly, intraperitoneal administration suppresses subcutaneously transplanted Suit-2 cells ameliorated decreased survival rate bearing mice, while co-administration ferrostatin-1 effect. We also partially showed ferroptotic effects on gemcitabine-resistant-PK cells, although its effect was exerted late compared treatment normal-PK cells. In addition, trial validate importance double bonds PUFAs revealed AA EPA had marked but DHA mild suppression proliferation. Furthermore, other lines sensitivity PUFA-induced ferroptosis; e.g., colorectal adenocarcinoma, or did not. Collectively, these data suggest can potential exert via both normal gemcitabine-resistant

Language: Английский

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Exocarpium Citri Grandis ameliorates LPS-induced acute lung injury by suppressing inflammation, NLRP3 inflammasome, and ferroptosis

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 329, P. 118162 - 118162

Published: April 7, 2024

Language: Английский

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The crosstalk between oncogenic signaling and ferroptosis in cancer

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 197, P. 104349 - 104349

Published: April 16, 2024

Language: Английский

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Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia

Antioxidants, Journal Year: 2024, Volume and Issue: 13(5), P. 591 - 591

Published: May 11, 2024

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension often accompanied proteinuria multiorgan dysfunction. It classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) late-onset preeclampsia (LO-PE). Despite being less severe exhibiting distinct pathophysiological characteristics, LO-PE more prevalent than EO-PE, although both conditions have significant impact placental health. Previous research indicates that different events within placenta may contribute to development across multiple pathways. In our experimental study, we investigated markers oxidative stress, ferroptosis, lipid peroxidation pathways in tissue samples obtained from women with (n = 68) compared healthy control pregnant (HC, n 43). Through comprehensive analysis, observed an upregulation specific molecules associated these pathways, including NADPH oxidase 1 (NOX-1), 2 (NOX-2), transferrin receptor protein (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase (GPX4) malondialdehyde (MDA) LO-PE. Furthermore, increased ferric deposition (Fe3+) was stained Perls’ Prussian blue. The assessment involved gene expression analyses conducted through RT-qPCR experiments immunohistochemistry assays. Our findings underscore heightened activation inflammatory HC, highlighting pathological mechanisms underlying this pregnancy disorder.

Language: Английский

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Fe₂O₃ Hollow Multishelled Structure Endowed Temporal Sequential Mass Release for Apoptosis/Ferroptosis‐Induced Combined Cancer Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Abstract Cisplatin (CDDP) combined with pemetrexed (MTA) is commonly employed in the treatment of advanced non‐small cell lung cancer. However, conventional clinical administration methods fail to achieve precise spatiotemporal delivery within tumor microenvironment (TME), resulting inadequate control local drug concentrations and impeding synergistic efficacy chemotherapeutic drugs. Aiming address this issue, Fe 2 O 3 hollow multi‐shelled structure (HoMS) nanocarriers spatiotemporally controlled release properties co‐encapsulated CDDP MTA into nanocarrier are developed. The confined provided by ‐HoMS enables a targeted temporal sequential tailored requirements. Furthermore, chemotherapy‐induced DNA damage leads apoptosis, accompanied substantial generation reactive oxygen species (ROS). disruption ROS homeostasis subsequently activates ferroptosis pathway mediated ‐HoMS. In summary, exhibits highly two drugs TME, HoMS further involved regulation ferroptosis, realizing triple system comprising CDDP‐MTA‐Fe 2+ thus significantly enhancing anti‐tumor against This study proposes novel approach for optimizing design, addressing challenge precisely tumors.

Language: Английский

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