Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Language: Английский

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Regulation of mammalian cellular metabolism by endogenous cyanide production

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Small, gaseous molecules such as nitric oxide, carbon monoxide and hydrogen sulfide are produced signalling in mammalian cells. Here, we show that low concentrations of cyanide generated endogenously various tissues We detect several cellular compartments human cells the blood mice. Cyanide production is stimulated by glycine, occurs at pH lysosomes requires peroxidase activity. When a specific rate, exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism proliferation, but impairs bioenergetics high concentrations. can modify cysteine residues via protein S -cyanylation, which detectable basally mice, increases response to glycine. Low-dose supplementation exhibits cytoprotective hypoxia reoxygenation models vitro vivo. Conversely, pathologically elevated nonketotic hyperglycinaemia detrimental Our findings indicate should be considered part same group endogenous regulatory gasotransmitters sulfide.

Language: Английский

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Protective Roles of Hydrogen Sulfide in Alzheimer’s Disease and Traumatic Brain Injury

Antioxidants, Journal Year: 2023, Volume and Issue: 12(5), P. 1095 - 1095

Published: May 13, 2023

The gaseous signaling molecule hydrogen sulfide (H2S) critically modulates a plethora of physiological processes across evolutionary boundaries. These include responses to stress and other neuromodulatory effects that are typically dysregulated in aging, disease, injury. H2S has particularly prominent role modulating neuronal health survival under both normal pathologic conditions. Although toxic even fatal at very high concentrations, emerging evidence also revealed pronounced neuroprotective for lower doses endogenously generated or exogenously administered H2S. Unlike traditional neurotransmitters, is gas and, therefore, unable be stored vesicles targeted delivery. Instead, it exerts its physiologic through the persulfidation/sulfhydration target proteins on reactive cysteine residues. Here, we review latest discoveries roles Alzheimer's disease (AD) traumatic brain injury, which one greatest risk factors AD.

Language: Английский

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Protein persulfidation: Rewiring the hydrogen sulfide signaling in cell stress response

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 209, P. 115444 - 115444

Published: Feb. 1, 2023

Language: Английский

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Label-Free, Reusable, Equipment-Free, and Visual Detection of Hydrogen Sulfide Using a Colorimetric and Fluorescent Dual-Mode Sensing Platform

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(14), P. 5920 - 5926

Published: March 29, 2023

In this work, we have found for the first time that fluorescence of rhodamine B (RhB) would be dramatically reduced after it bound to hemin/G-quadruplex and reacted with •OH. Based on finding, designed a colorimetric fluorescent dual-mode sensing platform visual detection hydrogen sulfide (H2S). The constructed sensor is based formation dsDNA G-quadruplex structure by cytosine-Ag+-cytosine mismatch, causing H2O2-mediated catalysis oxidize ABTS or RhB induce change. presence H2S, solution color assays change from dark green pink (fluorescence off) bright yellow on), respectively. This assay showed high selectivity toward H2S over other interference materials low measurable limit value (below than 2.5 μM), has been successfully applied in real samples. Moreover, strategy presented an excellent reutilization character both assays. method was employed as label-free, simple, fast, equipment-free reusability. work realized naked-eye analysis at lower concentration demonstrating promising on-site H2S.

Language: Английский

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Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation

Cell Metabolism, Journal Year: 2023, Volume and Issue: 36(1), P. 78 - 89.e5

Published: Dec. 18, 2023

Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H

Language: Английский

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Hydrogen sulfide donors across time: From origins to cutting-edge applications

Nitric Oxide, Journal Year: 2024, Volume and Issue: 144, P. 29 - 39

Published: Feb. 1, 2024

Language: Английский

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Signaling Paradigms of H2S-Induced Vasodilation: A Comprehensive Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1158 - 1158

Published: Sept. 25, 2024

Hydrogen sulfide (H

Language: Английский

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Fluorescent probes for detecting and imaging mitochondrial hydrogen sulfide

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: 407, P. 111328 - 111328

Published: Jan. 19, 2025

Language: Английский

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A Bioluminescent Probe for H₂S Detection in Tumor Microenvironment

ACS Bio & Med Chem Au, Journal Year: 2025, Volume and Issue: 5(1), P. 175 - 183

Published: Jan. 3, 2025

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule that regulates various physiological functions, and its abnormal levels have been closely linked to the onset progression of numerous diseases including renal cell carcinoma (RCC). RCC most common malignant tumor kidney, accounting for 85-90% all kidney cancer cases. However, studies using H2S as a biomarker monitoring at molecular level remain relatively limited. Most current luminescent probes suffer from low sensitivity often need external stimuli, such cysteine, artificially elevate levels, thereby reducing their effectiveness in detecting cells or vivo. Although bioluminescent imaging are gaining attention specificity high signal-to-noise ratio, no existing specifically designed RCC. Additionally, many face challenges short emission wavelengths dependence on complex conditions adenosine triphosphate (ATP). Herein, through "caging" luciferin substrate QTZ with recognition groups, H2S-sensitive probe QTZ-N3 good (∼0.19 μM) selectivity was prepared. can effectively detect 786-O-Nluc sensitively monitor xenograft nude mouse model without requiring stimuli like cysteine. Furthermore, allows real-time during progression. This work lays solid foundation future understanding biological functions

Language: Английский

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