Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury

Free Radical Biology and Medicine, Год журнала: 2020, Номер 160, С. 303 - 318

Опубликована: Авг. 23, 2020

Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of regulated cell death (RCD), playing critical roles in organ injury targeting therapy cancers. Previous studies have demonstrated that ferroptosis participates the development cardiomyopathy including cardiac hypertrophy, diabetic doxorubicin-induced cardiotoxicity. However, role sepsis-induced remains unclear. This study aimed to explore underlying mechanism on lipopolysaccharide (LPS)-induced injury. Mice were injected with LPS (10 mg/kg) for 12 h generate experimental sepsis. Ferrostatin-1 (Fer-1) Dexrazoxane (DXZ) used suppress mice increased levels ferroptotic markers involving prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA) lipid ROS, apart from resulting obvious mitochondria damage, which alleviated by Fer-1 DXZ. In vitro experiments showed inhibited LPS-induced peroxidation H9c2 myofibroblasts while erastin sorafenib aggravated ferroptosis. Additionally, DXZ improved survival rate function Mechanistically, expression nuclear receptor coactivator 4 (NCOA4) level intracellular Fe2+ but decreased ferritin. NCOA4 could directly interact ferritin degrade it ferritinophagy-dependent manner, subsequently released great amount iron. Cytoplasmic further activated siderofexin (SFXN1) mitochondrial membrane, turn transported cytoplasmic into mitochondria, giving rise production ROS Based these findings, we concluded ferritinophagy-mediated one mechanisms contributing Targeting cardiomyocytes may be therapeutic strategy preventing sepsis future.

Язык: Английский

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Mitochondrial regulation of ferroptosis

The Journal of Cell Biology, Год журнала: 2021, Номер 220(9)

Опубликована: Июль 30, 2021

Ferroptosis is a form of iron-dependent regulated cell death driven by uncontrolled lipid peroxidation. Mitochondria are double-membrane organelles that have essential roles in energy production, cellular metabolism, and regulation. However, their role ferroptosis has been unclear somewhat controversial. In this Perspective, I summarize the diverse metabolic processes mitochondria actively drive ferroptosis, discuss recently discovered mitochondria-localized defense systems detoxify mitochondrial peroxides protect against present new evidence for regulating outline outstanding questions on fascinating topic future investigations. An in-depth understanding functions will important implications both fundamental biology disease treatment.

Язык: Английский

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Ferroptosis, radiotherapy, and combination therapeutic strategies

Protein & Cell, Год журнала: 2021, Номер 12(11), С. 836 - 857

Опубликована: Апрель 23, 2021

Ferroptosis, an iron-dependent form of regulated cell death driven by peroxidative damages polyunsaturated-fatty-acid-containing phospholipids in cellular membranes, has recently been revealed to play important role radiotherapy-induced and tumor suppression, mediate the synergy between radiotherapy immunotherapy. In this review, we summarize known as well putative mechanisms underlying crosstalk ferroptosis, discuss interactions ferroptosis other forms induced radiotherapy, explore combination therapeutic strategies targeting This review will provide frameworks for future investigations cancer therapy.

Язык: Английский

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HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications

Cell Reports, Год журнала: 2020, Номер 33(10), С. 108487 - 108487

Опубликована: Дек. 1, 2020

Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cells exhibit enhanced resistance to ferroptotic damage induced common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) Erastin monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) deactivate energy sensor AMP-activated protein kinase (AMPK), leading upregulation sterol element-binding (SREBP1) downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) enhance anti-ferroptosis monounsaturated fatty acids. Additionally, blocking via hydroxycarboxylic acid receptor (HCAR1)/MCT1 inhibition promotes activating AMPK downregulate SCD1, which may synergize with acyl-coenzyme synthetase 4 (ACSL4)-promoting effect amplify susceptibility. vitro vivo evidence confirms regulates HCC highlights translational potential therapeutic target ferroptosis-based tumor treatment.

Язык: Английский

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Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis

Cell Metabolism, Год журнала: 2020, Номер 33(1), С. 174 - 189.e7

Опубликована: Дек. 22, 2020

Язык: Английский

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Ferroptosis and its emerging roles in cardiovascular diseases

Pharmacological Research, Год журнала: 2021, Номер 166, С. 105466 - 105466

Опубликована: Фев. 5, 2021

Язык: Английский

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Molecular mechanisms of ferroptosis and their involvement in brain diseases

Pharmacology & Therapeutics, Год журнала: 2023, Номер 244, С. 108373 - 108373

Опубликована: Март 8, 2023

Ferroptosis is a type of regulated cell death characterized by intracellular accumulation iron and reactive oxygen species, inhibition system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation lipid peroxidation. Since its discovery characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, involvement disease pathways. inducers include erastin, sorafenib, sulfasalazine glutamate, which, inhibiting prevent import cysteine into cells. RSL3, statins, Ml162 Ml210 induce ferroptosis peroxidase 4 (GPX4), which responsible for preventing formation peroxides, FIN56 withaferin trigger GPX4 degradation. On other side, inhibitors ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 BH4, interrupt peroxidation cascade. Additionally, deferoxamine, deferiprone N-acetylcysteine, targeting cellular pathways, also classified as inhibitors. Increased evidence has established distinct brain diseases, including Alzheimer's, Parkinson's Huntington's amyotrophic lateral sclerosis, multiple Friedreich's ataxia. Thus, deep understanding how contributes these it can be modulated, open new window opportunities novel therapeutic strategies targets. Other studies shown sensitivity cancer cells with mutated RAS induction that chemotherapeutic agents synergize tumor treatment. tempting consider may arise target mechanistic pathway treatment tumors. Therefore, this work provides an up-to-date review on molecular mechanisms their diseases. In addition, information main targets provided.

Язык: Английский

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Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment

Nanoscale, Год журнала: 2021, Номер 13(9), С. 4855 - 4870

Опубликована: Янв. 1, 2021

MR imaging-guided a synergistic ferroptosis-photodynamic therapy strategy can enhance antitumor effects by accumulating intracellular ROS through the utilization of iron-based nanoparticles.

Язык: Английский

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A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

Small, Год журнала: 2021, Номер 17(32)

Опубликована: Июль 3, 2021

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted the controlled and upregulated cellular antioxidant defense. To enhance ·OH-induced damage CDT, covalent organic framework (COF)-based, ferrocene (Fc)- glutathione peroxidase 4 (GPX4) inhibitor-loaded nanodrug, RSL3@COF-Fc (2b), fabricated. The obtained 2b not only promotes situ Fenton-like reactions to trigger ·OH production cells, but also attenuates repair mechanisms under oxidative stress via irreversible GPX4 inhibition. As result, these two synergistically result massive lipid peroxide accumulation, subsequent damage, ultimately ferroptosis, while being limited intracellular glutathione. It believed that this research provides paradigm for enhancing reactive oxygen species-mediated oncotherapy through redox dyshomeostasis may provide new insights developing COF-based nanomedicine.

Язык: Английский

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Ferroptosis and cardiovascular disease: role of free radical-induced lipid peroxidation

Free Radical Research, Год журнала: 2021, Номер 55(4), С. 405 - 415

Опубликована: Янв. 18, 2021

Cardiovascular disease (CVD), including heart attack, stroke, failure, arrhythmia, and other congenital diseases remain the leading cause of morbidity mortality worldwide. The deaths in CVD is attributed to myocardial infarction due rupture atherosclerotic plaque. Atherosclerosis refers a condition when restricted or even blockage blood flow occurs narrowing vessels as result buildup plaques composed oxidized lipids. It well-established that free radical oxidation polyunsaturated fatty acids (PUFAs) lipoproteins cell membranes, termed lipid peroxidation (LPO), plays significant role atherosclerosis. LPO products are involved immune responses this process, which previous evidence supports programmed death (apoptosis) necrosis. Ferroptosis newly identified form regulated characterized by iron-dependent accumulation hydroperoxides lethal levels, exhibits distinct features from apoptosis, necrosis autophagy morphology, biochemistry genetics. Emerging appears demonstrate ferroptosis also CVD. In review, we summarize recent progress on atherosclerosis, highlighting LPO. underlying challenges field will be critically discussed.

Язык: Английский

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