Oxidative Metabolism as a Cause of Lipid Peroxidation in the Execution of Ferroptosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7544 - 7544

Published: July 9, 2024

Ferroptosis is a type of nonapoptotic cell death that characteristically caused by phospholipid peroxidation promoted radical reactions involving iron. Researchers have identified many the protein factors are encoded genes promote ferroptosis. Glutathione peroxidase 4 (GPX4) key enzyme protects phospholipids from and suppresses ferroptosis in glutathione-dependent manner. Thus, dysregulation involved cysteine and/or glutathione metabolism closely associated with From perspective dynamics, actively proliferating cells more prone to than quiescent cells, which suggests species generated during oxygen-involved responsible for lipid peroxidation. Herein, we discuss initial events dominantly occur process energy metabolism, association deficiency. Accordingly, tricarboxylic acid cycle coupled respiratory chain mitochondria main subjects here, this likely source both electrons free Since not only carbohydrates, but also amino acids, especially glutamate, major substrates central dealing nitrogen derived groups contributes subject discussion.

Language: Английский

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Zero-Crosstalk Tumor-Targeting Ratiometric Near-Infrared γ-Glutamyltranspeptidase Probe for Fluorescent-Guided Surgical Resection of Orthotopic Hepatic Tumor

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

The challenge of "false positive" signals significantly complicates tumor localization and surgical resection, which are pivotal for successful surgeries. Therefore, the development a method preoperative intraoperative margin determination holds considerable promise improving outcomes. In this study, zero-crosstalk ratiometric tumor-targeting near-infrared (NIR) fluorescent probe was developed precise cancer diagnosis navigation via NIR fluorescence imaging. This integrates moiety that selectively homes in on hepatocellular carcinoma cells exhibits highly sensitive response to γ-glutamyltranspeptidase (GGT), characterized by substantial emission shift from 830 650 nm. unique property enhances its effectiveness early imaging-guided surgery resection. Furthermore, successfully monitors GGT activity blood, cells, vivo, endowing potential clinic. Due efficient targeting situ both subcutaneous tumors orthotopic hepatic tumors, accurate detection capability tumors. Additionally, leveraging imaging, can serve as sprayable tool delineating margins with precision, thereby furnishing real-time imaging guidance during resection surgery.

Language: Английский

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Developing and experimental validating a T cell senescence-related gene signature to predict prognosis and immunotherapeutic sensitivity in non-small cell lung cancer

Gene, Journal Year: 2025, Volume and Issue: unknown, P. 149233 - 149233

Published: Jan. 1, 2025

Language: Английский

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The role of potential oxidative biomarkers in the prognosis of intracerebral hemorrhage and the exploration antioxidants as possible preventive and treatment options

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 4, 2025

Intracerebral hemorrhage (ICH) is a non traumatic that occurs in certain part of the brain. It usually leads to brain cell damage. According large number experimental research, oxidative stress an important pathophysiological processes cerebral hemorrhage. In this paper, we aim determine how changes biomarkers indicate damage degree hemorrhage, and explore summarize potential treatments or interventions. We found patients with are characterized by increased levels markers, such as total malondialdehyde (MDA), F2 isoprostaglandin, hydroxynonenal, myeloperoxidase protein hydroxyl. Therefore, caused ICH on these markers can be used evaluate diagnose ICH, predict its prognosis, guide preventive treatment turn antioxidant based new alternative.

Language: Английский

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Metabolomics insights into the protective molecular mechanism of Vaccinium myrtillus against oxidative stress in intestinal cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Abstract Blueberry ( Vaccinium myrtillus L. ) is a rich source of secondary metabolites known for their potent antioxidant, anti-inflammatory, and cytoprotective properties. These compounds are essential in neutralizing reactive oxygen species (ROS), which implicated oxidative stress-related diseases. In this study, we induced stress IEC-6 small intestine cells using hydrogen peroxide (H 2 O ), creating cellular model to investigate the biochemical response. The obtained results showed that blueberry extract (BLUBE) significantly exhibited strong antioxidant capacity, as evidenced by DPPH, FRAP ABTS vitro tests. Additionally, BLUBE effectively inhibited release enhanced response, indicated improved wound healing clonogenic potential reduction fibers rearrangement apoptosis. Metabolomic analysis, specifically High-Resolution Mass Spectrometry (HR-MS), was employed elucidate metabolic alterations associated with protective activity against cells. Chemometric approaches were applied preprocess data, explore variability, identify systematic biases, ensuring removal batch effects other experimental artifacts. A Partial Least Squares Discriminant Analysis classification confirmed clear group stratifications high accuracy (98.75 ± 2.31%), sensitivity, specificity, aiding identification significant pathway enrichment analysis. Key pathways, including sphingolipid metabolism, taurine hypotaurine glycerophospholipid cysteine methionine modulated, supporting basis BLUBE’s effects. fact, able partially reverse downregulation these reducing promoting cell survival. This study highlights power HR-MS-based metabolomics uncovering mechanisms nutraceuticals emphasizes agent It also underscores growing significance food pharmaceutical industries.

Language: Английский

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Enhancing the Oral Bioavailability of Glutathione Using Innovative Analogue Approaches

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 385 - 385

Published: March 18, 2025

Background: Glutathione (GSH) is an essential antioxidant that protects against oxidative stress, but its oral bioavailability below 1% due to enzymatic degradation and poor gastrointestinal absorption. Improving the of GSH could significantly enhance therapeutic efficacy. Methods: This study synthesised analogues with chemical modifications improve bioavailability. Seven derivatives were designed: three altered stereochemistry (1.62, 1.63, 1.64) N-methylated (1.65, 1.70, 1.71), alongside a native (1.61). The via Fmoc-solid-phase peptide synthesis, they characterised using reverse-phase high-performance liquid chromatography (RP-HPLC), electrospray ionisation mass spectrometry (ESI-MS), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy. Their toxicity was assessed on Caco-2 cells for viability, their activity UVA-irradiated fibroblast cells, resistance, interactions GSH-metabolising enzymes. Results: Among tested analogues, cysteine Compound (1.70) emerged as most promising candidate. 1.70 demonstrated superior resistance degradation, well showing enhanced cell viability improved activity. In vivo studies revealed 16.8-fold increase in plasma half-life (t½) 16.1-fold compared GSH. Conclusions: Chemical modification strategies, particularly N-methylation GSH, present viable approach enhancing showed significant potential applications, warranting further investigation development clinical settings.

Language: Английский

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Redox remodeling of central metabolism as a driving force for cellular protection, proliferation, differentiation, and dysfunction

Free Radical Research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 24

Published: Sept. 24, 2024

The production of reactive oxygen species (ROS) is elevated

Language: Английский

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CNDP2: An Enzyme Linking Metabolism and Cardiovascular Diseases?

Journal of Cardiovascular Translational Research, Journal Year: 2024, Volume and Issue: 18(1), P. 48 - 57

Published: Sept. 30, 2024

Language: Английский

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CTD-Global (CTD-G): A novel composition, transition, and distribution based peptide sequence encoder for hormone peptide prediction

Informatics in Medicine Unlocked, Journal Year: 2024, Volume and Issue: 50, P. 101578 - 101578

Published: Jan. 1, 2024

Language: Английский

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Initial Glutathione Depletion During Short-Term Bed Rest: Pinpointing Synthesis and Degradation Checkpoints in the γ-Glutamyl Cycle

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1430 - 1430

Published: Nov. 21, 2024

Hypokinesia triggers oxidative stress and accelerates the turnover of glutathione system via γ-glutamyl cycle. Our study aimed to identify regulatory checkpoints controlling intracellular levels. We measured intermediate substrates cycle in erythrocytes from 19 healthy young male volunteers before during a 10-day experimental bed rest. Additionally, we tracked changes levels specific metabolite ratios up 21 days Using gas chromatography-mass spectrometry internal standard technique, observed 9 ± 9% decrease first 5 rest, followed by an 11 increase 5th 10th day, nearly returning baseline ambulatory The cysteinyl-glycine-to-glutathione ratio, reflecting cyclotransferase activity (a key enzyme breakdown), rose 14 22% then fell 10 14% over subsequent days, again approaching cysteine-to-cysteine indicative cysteine synthetase (crucial for synthesis), increased 12 30% on day 29 41% results rest confirm those seen 10. By calculating ratio product concentration precursor concentration, assessed efficiency these enzymes turnover. These were corroborated directly measuring synthesis degradation rates vivo using stable isotope techniques. findings reveal significant kinetics initial potential therapeutic targets maintaining

Language: Английский

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