BAP1 links metabolic regulation of ferroptosis to tumour suppression

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(10), P. 1181 - 1192

Published: Sept. 3, 2018

Language: Английский

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GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis

PROTEOMICS, Journal Year: 2019, Volume and Issue: 19(18)

Published: March 20, 2019

Abstract Oxygen is necessary for aerobic metabolism but can cause the harmful oxidation of lipids and other macromolecules. Oxidation cholesterol phospholipids containing polyunsaturated fatty acyl chains lead to lipid peroxidation, membrane damage, cell death. Lipid hydroperoxides are key intermediates in process peroxidation. The hydroperoxidase glutathione peroxidase 4 (GPX4) converts alcohols, this prevents iron (Fe 2+ )‐dependent formation toxic reactive oxygen species (ROS). Inhibition GPX4 function leads peroxidation result induction ferroptosis, an iron‐dependent, non‐apoptotic form This review describes species, preventing oxidative link between dysfunction, oxidation, ferroptosis.

Language: Английский

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Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion

Cell Death and Differentiation, Journal Year: 2019, Volume and Issue: 26(11), P. 2284 - 2299

Published: Feb. 8, 2019

Ferroptosis is a recently identified form of regulated cell death defined by the iron-dependent accumulation lipid reactive oxygen species. has been studied in various diseases such as cancer, Parkinson's disease, and stroke. However, exact function mechanism ferroptosis ischemia/reperfusion (I/R) injury, especially intestine, remains unknown. Considering unique conditions required for ferroptosis, we hypothesize that ischemia promotes immediately after intestinal reperfusion. In contrast to conventional strategies employed I/R studies, focused on ischemic phase. Here verified assessing proferroptotic changes along with protein peroxidation levels during The inhibition liproxstatin-1 ameliorated I/R-induced injury. Acyl-CoA synthetase long-chain family member 4 (ACSL4), which key enzyme regulates composition, shown contribute execution but its role needs clarification. present study, used rosiglitazone (ROSI) siRNA inhibit ischemia/hypoxia-induced ACSL4 vivo vitro. results demonstrated before reperfusion protected against death. Further investigation revealed special 1 (Sp1) was crucial transcription factor increased binding promoter region. Collectively, this study demonstrates closely associated critical lethal process. Sp1 an important promoting expression. These suggest effective mechanistic approach injury prevention treatment.

Language: Английский

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Ischemia/Reperfusion

Comprehensive physiology, Journal Year: 2016, Volume and Issue: unknown, P. 113 - 170

Published: Dec. 6, 2016

Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease death in westernized cultures. The extent tissue injury relates directly to blood flow reduction length ischemic period, which influence levels cellular ATP intracellular pH reduced. By impairing ATPase-dependent ion transport, ischemia mitochondrial calcium increase (calcium overload). Cell volume regulatory mechanisms also disrupted by lack ATP, can induce lysis organelle plasma membranes. Reperfusion, although required salvage oxygen-starved tissues, produces paradoxical responses that fuel production reactive oxygen species (oxygen paradox), sequestration proinflammatory immunocytes endoplasmic reticulum stress, development postischemic capillary no-reflow, amplify injury. These pathologic events culminate opening permeability transition pores a end-effector ischemia/reperfusion (I/R)-induced cell death. Emerging concepts include intestinal microbiome, fetal programming, epigenetic changes, microparticles pathogenesis I/R. overall goal this review is describe these other contribute I/R Because so many different deleterious participate I/R, it clear therapeutic approaches will be effective only when multiple processes targeted. In addition, translational significance research enhanced much wider use animal models incorporate complicating effects risk factors for cardiovascular disease. © 2017 American Physiological Society. Compr Physiol 7:113-170, 2017.

Language: Английский

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Polyamine metabolism and cancer: treatments, challenges and opportunities

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(11), P. 681 - 695

Published: Sept. 4, 2018

Language: Английский

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Ferroptosis: A Novel Anti-tumor Action for Cisplatin

Cancer Research and Treatment, Journal Year: 2017, Volume and Issue: 50(2), P. 445 - 460

Published: May 11, 2017

Purpose Ferroptosis is a new mode of regulated cell death, which completely distinct from other death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role ferroptosis in classic chemotherapy drugs, including underlying mechanism. Materials Methods Cell viabilitywas detected by using methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout iron-responsive element binding protein 2, polymerase chain reaction, western blot was evaluate efficiency. Intracellular reduced glutathione level peroxidases activitywere determined related assay kit. Intracellularreactive oxygen species levelswere flowcytometry. Electron microscopywas observe ultrastructure changes cell. Results Among five chemotherapeutic drugs screened this study, cisplatin found be an inducer for both apoptosis A549 HCT116 cells. The depletion caused inactivation peroxidase played vital Besides, combination therapy erastin showed significant synergistic effect their anti-tumor activity. Conclusion had great potential become approach therapies make up some open way utility clinic. Key words: Ferroptosis, Cisplatin, Erastin, Glutathione, Glutathione

Language: Английский

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FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation

Nature Chemical Biology, Journal Year: 2018, Volume and Issue: 14(5), P. 507 - 515

Published: March 29, 2018

Language: Английский

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Ferroptosis, a new form of cell death, and its relationships with tumourous diseases

Journal of Cellular and Molecular Medicine, Journal Year: 2016, Volume and Issue: 21(4), P. 648 - 657

Published: Nov. 10, 2016

Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis results iron-dependent lipid peroxide accumulation. Ferroptotic characterized by cytological changes, including volume shrinkage increased mitochondrial membrane density. can be induced two classes small-molecule substances known as class 1 (system Xc- inhibitors) 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these substances, number drugs (e.g. sorafenib, artemisinin its derivatives) induce ferroptosis. Various factors, such the mevalonate (MVA) sulphur-transfer pathways, play pivotal roles in regulation plays an unneglectable role regulating growth proliferation some types tumour cells, lymphocytoma, ductal cancer pancreas, renal carcinoma (RCC) hepatocellular (HCC). Here, we will first introduce discovery research pertaining ferroptosis; then summarize induction mechanisms regulatory pathways finally, further elucidate human tumourous diseases.

Language: Английский

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GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues

Antioxidants and Redox Signaling, Journal Year: 2017, Volume and Issue: 29(1), P. 61 - 74

Published: May 2, 2017

Iron-dependent lipid peroxidation is a complex oxidative process where phospholipid hydroperoxides (PLOOH) are produced in membranes and finally transformed into series of decomposition products, some which endowed with biological activity. It specifically prevented by glutathione peroxidase 4 (GPx4), the selenoenzyme that reduces PLOOH (GSH). both product major initiator peroxidative chain reactions, as well an activator lipoxygenases. α-Tocopherol breaks propagation inhibits Thus, GPx4, GSH, α-tocopherol integrated concerted anti-peroxidant mechanism. Recent Advances: Ferroptosis has been recently identified cell death subroutine activated missing GPx4 activity inhibited iron chelation or supplementation. induction may underlie spontaneous human diseases, such neurodegeneration neuroinflammation, causing excessive death. The basic mechanism ferroptosis, therefore, fits features activation peroxidation.Still lacking convincing proofs lipoxygenases involved ferroptosis. Also, unknown molecules eventually killing cells mechanisms underlying drop cellular capacity.Molecular events ferroptosis to be unraveled validated on animal models inactivation, role GSH concentration, increased availability, membrane structure composition. This expected drive drug discovery aimed at halting degenerative diseases boosting it cancer cells. Antioxid. Redox Signal. 29, 61-74.

Language: Английский

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From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy

Seminars in Cancer Biology, Journal Year: 2017, Volume and Issue: 46, P. 65 - 83

Published: March 1, 2017

Language: Английский

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