Targeting ferroptosis in acute kidney injury

Cell Death and Disease, Год журнала: 2022, Номер 13(2)

Опубликована: Фев. 24, 2022

Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As form of programmed cell death (PCD), ferroptosis could be considered as process iron accumulation enhanced lipid peroxidation. Recently, the fundamental roles in AKI have attracted much attention. The network mechanism its to chronic disease (CKD) transition complicated multifactorial. Strategies targeting show great potential. Here, we review research progress on participation AKI. We hope that this work will provide clues for further studies

Язык: Английский

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High Level of Uric Acid Promotes Atherosclerosis by Targeting NRF2-Mediated Autophagy Dysfunction and Ferroptosis

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 21

Опубликована: Апрель 18, 2022

Atherosclerotic vascular disease (ASVD) is the leading cause of death worldwide. Hyperuricemia fourth risk factor for atherosclerosis after hypertension, diabetes, and hyperlipidemia. The mechanism hyperuricemia affecting occurrence development has not been fully elucidated. Mononuclear macrophages play critical roles in all stages atherosclerosis. Studies have confirmed that both ferroptosis promote atherosclerosis, but whether high level uric acid (HUA) promotes by regulating remains unclear. We found HUA significantly promoted atherosclerotic plaque downregulated protein NRF2/SLC7A11/GPX4 signaling pathway ApoE-/- mice. Next, we evaluated effect inhibitor ferrostatin-1 (Fer-1) treatment on formation macrophage-derived foam cells. cells, decreased cell viability, increased iron accumulation lipid peroxidation treated with oxidized low-density lipoprotein (oxLDL); these effects were reversed Fer-1 treatment. Mechanistically, inhibited autophagy pathway. activated upregulated ferroptosis-associated proteins. Moreover, an NRF2 inducer (tertbutyl hydroquinone (TBHQ)) activator (rapamycin (RAPA)) could reverse inhibitory survival. Our results suggest HUA-induced involved plaques. More importantly, enhancing inhibiting activating may alleviate These findings might contribute to a deeper understanding role pathogenesis provide therapeutic target ASVD associated hyperuricemia.

Язык: Английский

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Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling

Medicinal Research Reviews, Год журнала: 2023, Номер 43(3), С. 614 - 682

Опубликована: Янв. 19, 2023

Abstract Ferroptosis is an iron‐dependent cell death program that characterized by excessive lipid peroxidation. Triggering ferroptosis has been proposed as a promising strategy to fight cancer and overcome drug resistance in antitumor therapy. Understanding the molecular interactions structural features of ferroptosis‐inducing compounds might therefore open door efficient pharmacological strategies against aggressive, metastatic, therapy‐resistant cancer. We here summarize mechanisms requirements small molecules target central players ferroptosis. Focus placed on (i) glutathione peroxidase (GPX) 4, only GPX isoenzyme detoxifies complex membrane‐bound hydroperoxides, (ii) cystine/glutamate antiporter system X c − for regeneration, (iii) redox‐protective transcription factor nuclear erythroid 2‐related (NRF2), (iv) GPX4 repression combination with induced heme degradation via oxygenase‐1. deduce common ferroptotic activity highlight challenges development. Moreover, we critically discuss potential natural products lead structures provide comprehensive overview structurally diverse biogenic bioinspired trigger iron oxidation, inhibition thioredoxin/thioredoxin reductase or less defined modes action.

Язык: Английский

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The mechanisms of ferroptosis and its role in atherosclerosis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116112 - 116112

Опубликована: Янв. 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.

Язык: Английский

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Regulated Necrosis in Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2022, Номер 42(11), С. 1283 - 1306

Опубликована: Сен. 22, 2022

During atherosclerosis, lipid-rich plaques are formed in large- and medium-sized arteries, which can reduce blood flow to tissues. This situation becomes particularly precarious when a plaque develops an unstable phenotype prone rupture. Despite advances identifying treating vulnerable plaques, the mortality rate disability caused by such lesions remains number one health threat developed countries. Vulnerable, characterized large necrotic core, implying prominent role for cell death atherosclerosis destabilization. Necrosis occur accidentally or be induced tightly regulated pathways. Over past decades, different forms of necrosis, including necroptosis, ferroptosis, pyroptosis, secondary have been identified, these may play important during atherogenesis. In this review, we describe several necrosis that how pharmacological modulation pathways stabilize plaques. Moreover, some challenges targeting as presence multiple death-inducing stimuli extensive cross-talk between discussed. A better understanding (regulated) mechanisms contributing destabilization open doors novel strategies will enable clinicians tackle residual cardiovascular risk many patients.

Язык: Английский

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Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

Phytotherapy Research, Год журнала: 2023, Номер 37(9), С. 3951 - 3963

Опубликована: Июнь 21, 2023

Abstract Vascular endothelial cells (VECs) are located between the blood plasma and vascular tissue, ferroptosis (iron‐dependent programmed cell death) of VECs can lead to a range cardiovascular diseases. Icariin is main active ingredient Epimedium brevicornum Maxim., which improve dysfunction. In present study, protective effects icariin on oxidised low‐density lipoprotein (ox‐LDL)‐treated high‐fat diet‐fed Apolipoprotein E‐deficient mice were investigated. Inflammatory fibrosis in tissues inflammatory factors serum supernatants detected, mitochondrial membrane potential expression levels ferroptosis‐associated proteins also detected. The results revealed that reduced atherosclerotic plaque area collagen fibres aortic sinus increased viability potential, whereas it reactive oxygen species VECs. nucleation transcription factor EB (TFEB) subsequent autophagy negatively associated with cells, more prominent autophagy, lower ferroptosis. Furthermore, by co‐treating two inhibitors, Bafilomycin A1 (blocking autophagosome lysosome fusion) 3‐methyladenine formation), respectively, promoting found be mediated through process autophagosome–lysosome fusion. vivo experiments, ferroptosis, alleviated lesions rate TFEB nucleation. Additionally, was ARG304, THR308 GLN311 optimal binding sites for interaction TFEB. Taken together, these suggest fusion autophagosomes lysosomes promoted icarrin enhances thus reduces Therefore, may candidate prevention and, thus, treatment

Язык: Английский

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Gualou-Xiebai herb pair ameliorate atherosclerosis in HFD-induced ApoE−/− mice and inhibit the ox-LDL-induced injury of HUVECs by regulating the Nrf2-mediated ferroptosis

Journal of Ethnopharmacology, Год журнала: 2024, Номер 326, С. 117892 - 117892

Опубликована: Фев. 11, 2024

Язык: Английский

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Nrf2-mediated ferroptosis inhibition: a novel approach for managing inflammatory diseases

Inflammopharmacology, Год журнала: 2024, Номер 32(5), С. 2961 - 2986

Опубликована: Авг. 10, 2024

Язык: Английский

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Berberine as a novel ACSL4 inhibitor to suppress endothelial ferroptosis and atherosclerosis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117081 - 117081

Опубликована: Июль 5, 2024

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process cell injury through ferroptosis, has potential to ameliorate damage. In this study, we aimed investigate berberine (BBR) as ACSL4 order suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created ApoE

Язык: Английский

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Puerarin Attenuates Iron Overload‐Induced Ferroptosis in Retina through a Nrf2‐Mediated Mechanism

Molecular Nutrition & Food Research, Год журнала: 2024, Номер 68(4)

Опубликована: Янв. 9, 2024

Scope Age‐related increases in retinal iron are involved the development of degeneration. The recently discovered iron‐dependent mechanism cell death known as ferroptosis has been linked to a wide range pathologies. However, its role overload‐induced degeneration is still uncertain. Puerarin associated with protection. purpose this research determine how puerarin prevents under overload conditions. Methods and results Models Kunming mice, 661W cell, ARPE‐19 established. Increased deposition significantly worsens pathology, decreases viability, induces ferroptotic changes. mitigates by decreasing excessive through regulation handling proteins lowering lipid peroxidation inhibition cyclooxygenase 2 expression activation nuclear factor‐E2‐related factor (Nrf2) signaling pathway downstream ferroptosis‐related (solute carrier family 7 member 11, glutathione peroxidase 4 heme oxygenase‐1). protective effect on diminished Nrf2‐specific inhibitor ML385. Conclusion These findings suggest targeting may be novel strategy for management exert some ocular benefits attenuating ferroptosis.

Язык: Английский

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