<p>The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy</p>

OncoTargets and Therapy, Год журнала: 2020, Номер Volume 13, С. 5429 - 5441

Опубликована: Июнь 1, 2020

Abstract: Erastin was initially discovered as a small molecule compound that selectively kills tumor cells expressing ST and RAS V12 later widely investigated an inducer of ferroptosis. Ferroptosis is recently form cell death caused by peroxidation induced the accumulation intracellular lipid reactive oxygen species (L-ROS) in iron-dependent manner. can mediate ferroptosis through variety molecules including cystine-glutamate transport receptor (system X C − ), voltage-dependent anion channel (VDAC), p53. able to enhance sensitivity chemotherapy radiotherapy, suggesting promising future cancer therapy. We hope this review will help better understand role erastin lay foundation for further research development erastin-based therapies future. Keywords: erastin, ferroptosis, system , p53, VDAC,

Язык: Английский

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Regulators of the transsulfuration pathway

British Journal of Pharmacology, Год журнала: 2018, Номер 176(4), С. 583 - 593

Опубликована: Июль 14, 2018

The transsulfuration pathway is a metabolic where transfer of sulfur from homocysteine to cysteine occurs. leads the generation several metabolites, which include cysteine, GSH and gaseous signalling molecule hydrogen sulfide (H

Язык: Английский

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Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Июнь 28, 2021

Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that decline of physical function often initiates by cell senescence organ ageing. Epigenetic dynamics immunometabolic reprogramming link to alterations cellular response intrinsic extrinsic stimuli, representing current hotspots as they not only (re-)shape individual identity, but also involve fate decision. This review focuses on present findings emerging concepts epigenetic, inflammatory, metabolic regulations consequences process. Potential therapeutic interventions targeting regulatory mechanisms, using state-of-the-art techniques are discussed.

Язык: Английский

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Cysteine and homocysteine as biomarker of various diseases

Food Science & Nutrition, Год журнала: 2020, Номер 8(9), С. 4696 - 4707

Опубликована: Авг. 12, 2020

Abstract Cysteine and homocysteine (Hcy), both sulfur‐containing amino acids (AAs), produced from methionine another acid, which is converted to Hcy further cysteine. This article aims highlight the link between cysteine Hcy, their mechanisms, important functions, play in body role as a biomarker for various types of diseases. So that using biomarker, we can prevent diagnose many review concluded hyperhomocysteinemia (elevated levels homocysteine) considered toxic cells associated with different health problems. Hyperhomocysteinemia low diseases like cardiovascular (CVD), ischemic stroke, neurological disorders, diabetes, cancer lung colorectal cancer, renal dysfunction‐linked conditions, vitiligo.

Язык: Английский

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Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases

Redox Biology, Год журнала: 2021, Номер 42, С. 101901 - 101901

Опубликована: Фев. 21, 2021

Generation of reactive oxygen species and related oxidants is an inevitable consequence life. Proteins are major targets for oxidation reactions, because their rapid reaction rates with high abundance in cells, extracellular tissues, body fluids. Additionally, oxidative stress able to degrade lipids carbohydrates highly intermediates, which eventually attack proteins at various functional sites. Consequently, a wide variety distinct posttranslational protein modifications formed by oxidation, glycoxidation, lipoxidation. Reversible relevant physiological processes constitute signaling mechanisms ("redox signaling"), while non-reversible may contribute pathological situations several diseases. A rising number publications provide evidence involvement the onset progression diseases as well aging processes. Certain products chemically stable large quantity, makes them promising candidates become biomarkers damage. Moreover, progress development detection quantification methods facilitates analysis time effort contributes future applicability clinical routine. The present review outlines most important classes selected examples modifications, elucidates chemistry beyond formation discusses available analysis. Furthermore, relevance potential context disease summarized.

Язык: Английский

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Hydrogen sulfide is neuroprotective in Alzheimer’s disease by sulfhydrating GSK3β and inhibiting Tau hyperphosphorylation

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(4)

Опубликована: Янв. 11, 2021

Alzheimer's disease (AD), the most common cause of dementia and neurodegeneration in elderly, is characterized by deterioration memory executive motor functions. Neuropathologic hallmarks AD include neurofibrillary tangles (NFTs), paired helical filaments, amyloid plaques. Mutations microtubule-associated protein Tau, a major component NFTs, its hyperphosphorylation AD. We have shown that signaling gaseous molecule hydrogen sulfide (H2S) dysregulated during aging. H2S signals via posttranslational modification termed sulfhydration/persulfidation, which participates diverse cellular processes. Here we show cystathionine γ-lyase (CSE), biosynthetic enzyme for H2S, binds wild type enhances catalytic activity. By contrast, CSE fails to bind Tau P301L, mutant present 3xTg-AD mouse model further depleted mice as well human brains, prevents sulfhydrating kinase, glycogen synthase kinase 3β (GSK3β). Finally, demonstrate sulfhydration diminished AD, while administering donor sodium GYY4137 (NaGYY) ameliorates cognitive deficits

Язык: Английский

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Simultaneous Visualization of Endogenous Homocysteine, Cysteine, Glutathione, and their Transformation through Different Fluorescence Channels

Angewandte Chemie International Edition, Год журнала: 2019, Номер 58(14), С. 4557 - 4561

Опубликована: Фев. 11, 2019

Abstract Studying numerous biologically important species simultaneously is crucial to understanding cellular functions and the root causes of related diseases. Direct visualization endogenous biothiols in biological systems great value their roles. Herein, a novel multi‐signal fluorescent probe was rationally designed exploited for simultaneous sensing homocysteine (Hcy), cysteine (Cys), glutathione (GSH) using different emission channels. This successfully applied discrimination between Hcy, Cys, GSH, transformation living cells.

Язык: Английский

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Stem Cell Factor SOX2 Confers Ferroptosis Resistance in Lung Cancer via Upregulation of SLC7A11

Cancer Research, Год журнала: 2021, Номер 81(20), С. 5217 - 5229

Опубликована: Авг. 12, 2021

Abstract Ferroptosis is a lipid peroxidation-dependent cell death caused by metabolic dysfunction. Ferroptosis-associated enzymes are promising therapeutic targets for cancer treatment. However, such strategies show limited efficacy due to drug resistance and other largely unknown underlying mechanisms. Here we report that cystine transporter SLC7A11 upregulated in lung stem-like cells (CSLC) can be activated stem transcriptional factor SOX2. Mutation of SOX2 binding site promoter reduced expression increased sensitivity ferroptosis cells. Oxidation at Cys265 inhibited its activity decreased the self-renewal capacity CSLCs. Moreover, tumors with high were more resistant ferroptosis, was positively correlated both mouse human tissue. Together, our study provides mechanism which evade suggests oxidation potential target Significance: This uncovers SOX2–SLC7A11 regulatory axis confers

Язык: Английский

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The Chemical Biology of Ferroptosis in the Central Nervous System

Cell chemical biology, Год журнала: 2020, Номер 27(5), С. 479 - 498

Опубликована: Апрель 2, 2020

Язык: Английский

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NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications

Chemical Society Reviews, Год журнала: 2021, Номер 50(13), С. 7436 - 7495

Опубликована: Янв. 1, 2021

Compounds with a nitrobenzoxadiazole (NBD) skeleton exhibit high reactivity toward biological nucleophilies accompanied by distinct colorimetric and fluorescent changes, environmental sensitivity, small size, all of which facilitate biomolecular sensing self-assembly.

Язык: Английский

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