Oxidative Stress and Its Role in Cd-Induced Epigenetic Modifications: Use of Antioxidants as a Possible Preventive Strategy

Oxygen, Journal Year: 2022, Volume and Issue: 2(2), P. 177 - 210

Published: May 29, 2022

Oxidative stress (OS) represents one of the main mechanisms toxicity induced by environmental pollutants such as cadmium (Cd). OS is a natural physiological process where presence oxidants, reactive oxygen-derived species (ROS), outweighs strategy antioxidant defenses, culminating in interruption signaling and redox control. It has been suggested that Cd increases ROS mainly inducing damage to electron transport chain increasing activity nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) oxidase (NOX) concentration free iron (Fe), well causing decrease defense. On other hand, related changes biology epigenome, adverse health effects. Recent studies show generates alterations deoxyribonucleic acid (DNA) methylation, histone modifications, noncoding RNA (ncRNA) expression. However, role Cd-induced epigenetic modifications still poorly explored. Therefore, this review provides an update on basic concepts its relationship with changes. Furthermore, use compounds proposed mitigate alterations.

Language: Английский

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Long-Term Stability Prediction for Developability Assessment of Biopharmaceutics Using Advanced Kinetic Modeling

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(2), P. 375 - 375

Published: Feb. 8, 2022

A crucial aspect of pharmaceutical development is the demonstration long-term stability drug product. Biopharmaceuticals, such as proteins or peptides in liquid formulation, are typically administered via parental routes and should be stable over shelf life, which generally includes a storing period (e.g., two years at 5 °C) optionally an in-use 28 days 30 °C). Herein, we present case study where chemical degradation SAR441255, therapeutic peptide, different formulations combination with primary packaging materials was analyzed under accelerated conditions to derive predictions for recommended (two °C plus using advanced kinetic modeling. These served decision parameter entry into clinical development. Comparison analytical data measured during subsequent phase demonstrated high prediction accuracy. provided insights within weeks that would otherwise take measurements only. To our knowledge, silico studies on peptide modeling comparisons subsequently real-life have not been described literature before.

Language: Английский

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Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Published: Feb. 13, 2024

The extracellular matrix (ECM) provides structural support for tissues and regulatory signals resident cells. ECM requires a careful balance between protein accumulation degradation homeostasis. Disruption of this can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications proteins collagens alter structure function. Dysregulation enzymes well changes composition are prevalent fibrosis. Because crucial roles that pathways play disease, govern events being explored therapeutic targets Here we review in-depth molecular mechanisms underlying crosslinking, how contributes fibrosis, strategies target restore normal tissue

Language: Английский

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Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

The aggregation of α-synuclein is crucial to the development Lewy body diseases, including Parkinson's disease and dementia with bodies. pathway typically involves a defined sequence nucleation, elongation, secondary exhibiting prion-like spreading. This study employed Raman spectroscopy machine learning analysis, alongside complementary techniques, characterize biomolecular changes during fibrillation purified recombinant wild-type protein. Monomeric was produced, purified, subjected 7-day assay generate preformed fibrils. Stages were analyzed using spectroscopy, confirmed through negative staining transmission electron microscopy, mass spectrometry, light scattering analyses. A pipeline incorporating principal component analysis uniform manifold approximation projection used analyze spectral data identify significant peaks, resulting in differentiation between sample groups. Notable shifts found various stages aggregation. Early (D1) included increases α-helical structures (1303, 1330 cm–1) β-sheet formation (1045 cm–1), reductions COO– CH2 bond regions (1406, 1445 cm–1). By D4, these structural persist additional features. At D7, decrease H-bonding (1625 tyrosine ring breathing (830 indicates further stabilization, suggesting shift from initial helical stabilized β-sheets aggregated Additionally, alterations peaks related tyrosine, alanine, proline, glutamic acid identified, emphasizing role amino acids intramolecular interactions transition conformational states fibrillation. approach offers insight into aggregation, enhancing understanding its pathophysiology potential diagnostic relevance.

Language: Английский

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Enzymes of glycolysis and the pentose phosphate pathway as targets of oxidants: role of redox reactions on the carbohydrate catabolism

Redox Biochemistry and Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 100049 - 100049

Published: Feb. 1, 2025

Language: Английский

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Oxidation products of proteins in plasma of newborns reflect damage inflicted by O2 supplementation and correlate with gestational age

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Inactivation of human glucose 6-phosphate dehydrogenase (G6PDH) by peroxyl radicals is strongly modulated by its substrate and cofactor

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Intramolecular Histidine Cross-Links Formed via Copper-Catalyzed Oxidation of Histatin Peptides

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Histidine is a versatile amino acid with metal-binding, nucleophilic, and basic properties that endow many peptides proteins biological activity. However, histidine itself susceptible to oxidative modifications via post-translational modifications, photo-oxidation, metal-catalyzed oxidation. Despite multiple investigations into these different oxidation systems, the varied attributions differential outcomes point significant gaps in our understanding of coordination requirements, spectral features, reaction products accompany Cu-catalyzed histidine-containing peptides. Here, we use model Histatin-5, salivary peptide Cu-potentiated antifungal activity relies on its residues, characterize complex mixture resulting from Cu under physiologically relevant reducing oxidizing conditions. Characterization LC-MS, MS/MS, UV-vis, NMR revealed adjacent residues bis-His site are main target oxidation, predominant being 2-oxo-His His-His cross-links give rise distinctive electronic absorption features between 300-400 nm. Doubly- triply-oxygenated peptides, intramolecular cross-links, multimers case shorter were also observed. The configuration motif may enable reactivity not available systems where His sequence or space. These results expand possibilities other containing histidines.

Language: Английский

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Inactivation of mitochondrial pyruvate dehydrogenase by singlet oxygen involves lipoic acid oxidation, side-chain modification and structural changes

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The multi-subunit pyruvate dehydrogenase complex (PDC) plays a crucial role in glucose oxidation as it determines whether is used for mitochondrial oxidative phosphorylation or converted to lactate aerobic glycolysis. PDC contains three lipoic acid groups, covalently attached at lysine residues give lipoyllysine, which are responsible acyl group transfer and critical activity. We have recently reported that both free acid, lipoyllysine alpha-keto glutarate dehydrogenase, highly susceptible singlet oxygen (1O2)-induced oxidation. therefore hypothesized activity structure would be influenced by 1O2 (generated using Rose Bengal light) via modification of the lipoyllysines other residues. was decreased photooxidation, with this being dependent on light exposure, O2, presence Bengal, D2O consistent 1O2-mediated reactions. These changes were modulated pre-illumination addition lipoamide. Activity loss occurred concurrently sidechain (determined mass spectrometry) protein aggregation (detected SDS-PAGE). Peptide mapping provided evidence 42 (Met, Trp, His Tyr; extents 20-50%) each sites (6-20% modification). Structure modelling indicated modifications occur across all 4 subunit types, functional domains multimer interfaces, damage multiple contributing overall data indicate 1O2-induced potential effects cellular pathways metabolism.

Language: Английский

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Hypothiocyanite and host–microbe interactions

Molecular Microbiology, Journal Year: 2023, Volume and Issue: 119(3), P. 302 - 311

Published: Jan. 31, 2023

The pseudohypohalous acid hypothiocyanite/hypothiocyanous (OSCN- /HOSCN) has been known to play an antimicrobial role in mammalian immunity for decades. It is a potent oxidant that kills bacteria but non-toxic human cells. Produced from thiocyanate (SCN- ) and hydrogen peroxide (H2 O2 variety of body sites by peroxidase enzymes, HOSCN explored as agent food preservation, pathogen killing, even improved toothpaste. However, despite the well-recognized antibacterial plays host-pathogen interactions, little about how sense respond this oxidant. In work, we will summarize what unknown innate recent advances understanding responses both pathogenic non-pathogenic mount against agent, highlighting studies done with three model organisms, Escherichia coli, Streptococcus spp., Pseudomonas aeruginosa.

Language: Английский

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