Fundamentals of redox regulation in biology

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(9), P. 701 - 719

Published: April 30, 2024

Language: Английский

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Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection

Antioxidants, Journal Year: 2024, Volume and Issue: 13(5), P. 504 - 504

Published: April 23, 2024

Despite the significant progress in fields of biology, physiology, molecular medicine, and pharmacology; designation properties nitrogen monoxide regulation life-supporting functions organism; numerous works devoted to this molecule, there are still many open questions field. It is widely accepted that nitric oxide (•NO) a unique molecule that, despite its extremely simple structure, has wide range body, including cardiovascular system, central nervous system (CNS), reproduction, endocrine respiration, digestion, etc. Here, we systematize •NO, contributing conditions physiological norms, as well various pathological processes, mechanisms cytoprotection cytodestruction. Current experimental clinical studies contradictory describing role •NO pathogenesis diseases CNS. We describe cytoprotective action associated with expression antiapoptotic chaperone proteins mitochondrial function. The most prominent cytodestruction—the initiation nitrosative oxidative stresses, production reactive oxygen species, participation apoptosis mitosis. formation endothelial dysfunction also considered. Moreover, focus on ways pharmacological modulation nitroxidergic allow for decrease cytodestructive increase ones.

Language: Английский

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Orthogonal Translation for Site-Specific Installation of Post-translational Modifications

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2805 - 2838

Published: Feb. 19, 2024

Post-translational modifications (PTMs) endow proteins with new properties to respond environmental changes or growth needs. With the development of advanced proteomics techniques, hundreds distinct types PTMs have been observed in a wide range from bacteria, archaea, and eukarya. To identify roles these PTMs, scientists applied various approaches. However, high dynamics, low stoichiometry, crosstalk between make it almost impossible obtain homogeneously modified for characterization site-specific effect individual PTM on target proteins. solve this problem, genetic code expansion (GCE) strategy has introduced into field studies. Instead modifying after translation, GCE incorporates amino acids during thus generating site-specifically at positions. In review, we summarize systems orthogonal translation installation PTMs.

Language: Английский

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Peroxynitrite: a multifaceted oxidizing and nitrating metabolite

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 80, P. 102459 - 102459

Published: May 8, 2024

Language: Английский

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Histone oxidation as a new mechanism of metabolic control over gene expression

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(9), P. 739 - 746

Published: June 23, 2024

Language: Английский

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Quantitative analysis of the proteome and protein oxidative modifications in primary human coronary artery endothelial cells and associated extracellular matrix

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103524 - 103524

Published: Feb. 7, 2025

Vascular endothelial cells (ECs) play a key role in physiology by controlling arterial contraction and relaxation, molecular transport. EC dysfunction is associated with multiple pathologies. Here, we characterize the cellular extracellular matrix (ECM) proteomes of primary human coronary artery ECs, from donors, oxidation/nitration products formed on these during cell culture, using liquid chromatography-mass spectrometry. In total ∼9900 proteins were identified 3 ∼7000 per donor. Of ∼5300 consistently identified, indicating some heterogeneity across age possible cause. Multiple endogenous oxidation detected both ECM (and particularly endoplasmic reticulum species). contrast, nitration was mostly cytoskeletal proteins, consistent intracellular generation nitrating agents, possibly nitric oxide synthase (eNOS) or peroxidase enzymes. The modifications are ascribed to physiological enzymatic activity (hydroxylation at proline/lysine; predominantly especially collagens) formation reactive species (oxidation tryptophan/tyrosine/histidine; tryptophan/tyrosine). sites present limited number peptides (104 oxidized; 23 nitrated) modest proteins. A small modifications, being selective specific targets. Several nitrated all also smooth muscle suggesting that major targets vascular proteome. These data provide 'background' proteome dataset for studies disease.

Language: Английский

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Protein Nitration in Patients with Mitochondrial Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 211 - 211

Published: Feb. 12, 2025

Mitochondrial diseases are complex disorders caused by nuclear or mitochondrial DNA mutations, leading to oxidative phosphorylation deficiency and excessive production of reactive oxygen species (ROS). While ROS have been well established in the pathogenesis these diseases, role nitrogen (RNS) remains unclear. In this study, we performed a quantitative analysis muscle fibers investigate relationship between protein nitration abnormalities (mitochondrial proliferation cytochrome-c oxidase (COX) deficiency) factors like genotype, damage, age. A total 1961 (303 from 4 controls 1658 29 patients with diseases) were analyzed immunostaining for nitro-tyrosine. Contrary previous findings, which identified nitro-tyrosine only small vessels, observed broader distribution affecting sarcolemma sarcoplasm. Using multivariate techniques, significant correlation but found no associations COX deficiency, age, genotype. These findings suggest that nitrative stress may contribute dysfunction play signaling processes induce biogenesis. Our results provide new insights into molecular mechanisms highlight potential relevance nitration.

Language: Английский

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Peroxisomal H2O2-generating sulfite oxidase (SOX) from pepper fruits is negatively modulated by NO and H2S

Plant Physiology and Biochemistry, Journal Year: 2025, Volume and Issue: 221, P. 109591 - 109591

Published: Feb. 12, 2025

Language: Английский

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SIRT1: A likely key for future therapeutic strategies for pain management

Pharmacological Research, Journal Year: 2025, Volume and Issue: 213, P. 107670 - 107670

Published: Feb. 20, 2025

Sirtuin 1 (SIRT1), a NAD+ -dependent histone deacetylase, plays crucial role in mitigating oxidative stress, regulating inflammation, and maintaining mitochondrial function. Reduced SIRT1 activity has been linked to elevated pro-inflammatory cytokines, dysfunction, chronic pain, all of which are observed long COVID pathology. Emerging evidence identifies dysfunction stress as central contributors these symptoms. Increases reactive oxygen species (ROS) such superoxide, nitric oxide, peroxynitrite, leading damage, central/peripheral sensitization. Nutraceuticals, particularly the polyphenolic fraction bergamot (BPF), have demonstrated potent antioxidant, anti-inflammatory, antiviral properties. This study highlights BPF's ability modulate rat model inflammation hyperalgesia. It provides novel nitration within nucleus key event inflammatory pain pathogenesis. BPF administration preserved activity, reduced markers malondialdehyde (MDA) 8-hydroxydeoxyguanosine (8-OHdG), minimized post-translational modifications nuclear proteins, including nitration, acetylation, carbonylation. Additionally, it alleviated hyperalgesia allodynia. These findings underscore therapeutic potential polyphenols like reducing inflammation-driven pain. By activating SIRT1, may provide relief for conditions. Further research on SIRT1-targeted therapies is essential combat preventing conditions enhancing treatment options.

Language: Английский

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The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1910 - 1910

Published: Feb. 23, 2025

Reductive stress (RS), characterized by excessive accumulation of reducing equivalents such as NADH and NADPH, is emerging a key factor in metabolic disorders cancer. While oxidative (OS) has been widely studied, RS its complex interplay with endocrine regulation remain less understood. This review explores molecular circuits bidirectional crosstalk between hormones RS, focusing on their role diabetes, obesity, cardiovascular diseases, disrupts insulin secretion signaling, exacerbates inflammation, contributes to adipose tissue dysfunction, ultimately promoting resistance. In alters vascular smooth muscle cell function myocardial metabolism, influencing ischemia-reperfusion injury outcomes. cancer, plays dual role: it enhances tumor survival buffering OS reprogramming, yet can trigger proteotoxicity mitochondrial leading apoptosis. Recent studies have identified RS-targeting strategies, including redox-modulating therapies, nanomedicine, drug repurposing, offering potential for novel treatments. However, challenges remain, particularly distinguishing physiological from pathological conditions overcoming therapy-induced Future research should focus developing selective biomarkers, optimizing therapeutic interventions, exploring the immune regulation.

Language: Английский

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