In pursuit of feedback activation: New insights into redox-responsive hydropersulfide prodrug combating oxidative stress DOI Creative Commons

Bi‐Xin Xu,

Tian-Yu Hu,

Jin-Biao Du

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103130 - 103130

Published: March 22, 2024

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient (RSSH) supply thoroughly explore their biological therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), canonical antioxidant enzyme, NQO1-activated RSSH prodrugs. We also performed head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis prodrugs, RSSH, metabolic by-products LC-MS/MS, confirming that the perthiocarbamate scaffold was effective intracellular prodrug uptake production. The highly potent stress management against cisplatin-induced nephrotoxicity. Strikingly, this possessed potential feedback properties which delivered can further escalate via NQO1 upregulation. Our strategy pushed one step pursuit release matrices improved druggability stress.

Language: Английский

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation DOI Creative Commons

Dunja Petrovic,

Luke Slade, Yiorgos Paikopoulos

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

2
Regulation of mammalian cellular metabolism by endogenous cyanide production DOI Creative Commons
Karim Zuhra, Maria Petrosino, Lucia Janickova

et al.

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

Citations

2
Longevity control by supersulfide-mediated mitochondrial respiration and regulation of protein quality DOI Creative Commons
Akira Nishimura,

Sunghyeon Yoon,

Tetsuro Matsunaga

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 69, P. 103018 - 103018

Published: Jan. 3, 2024

Supersulfides, which are defined as sulfur species with catenated atoms, increasingly being investigated in biology. We recently identified pyridoxal phosphate (PLP)-dependent biosynthesis of cysteine persulfide (CysSSH) and related supersulfides by cysteinyl-tRNA synthetase (CARS). Here, we the physiological role CysSSH budding yeast (Saccharomyces cerevisiae) generating a PLP-binding site mutation K109A CRS1 (the ortholog CARS), decreased synthesis also led to reduced chronological aging, effects that were associated an increased endoplasmic reticulum stress response impaired mitochondrial bioenergetics. Reduced aging mutant could be rescued using exogenous supersulfide donors. Our findings indicate important roles for CARS production metabolism supersulfides—to mediate function regulate longevity.

Language: Английский

Citations

9
Chemoselective Proteomics, Zinc Fingers, and a Zinc(II) Model for H2S Mediated Persulfidation DOI

Andrew T. Stoltzfus,

Jasper G. Ballot,

Thibaut Vignane

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(27)

Published: May 29, 2024

The gasotransmitter hydrogen sulfide (H

Language: Английский

Citations

9
Dual Roles of Reducing Systems in Protein Persulfidation and Depersulfidation DOI Creative Commons
Zhichao Liu, Nicolas Rouhier, Jérémy Couturier

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 101 - 101

Published: Jan. 16, 2025

The oxidative modification of specific cysteine residues to persulfides is thought be the main way by which hydrogen sulfide (H2S) exerts its biological and signaling functions. Therefore, protein persulfidation represents an important thiol-switching mechanism as other reversible redox post-translational modifications. Considering their reductase activity but also connections with proteins that generate H2S related molecules, glutaredoxin (GRX) thioredoxin (TRX)-reducing systems have potential dual roles in both depersulfidation. In this review, we will first focus on recent advances describing physiological pathways leading before discussing TRX glutathione/GRX-reducing persulfidation/depersulfidation.

Language: Английский

Citations

1
Neurobehavioral dysfunction in a mouse model of Down syndrome: upregulation of cystathionine β-synthase, H2S overproduction, altered protein persulfidation, synaptic dysfunction, endoplasmic reticulum stress, and autophagy DOI Creative Commons

Theodora Panagaki,

Lucia Janickova,

Dunja Petrovic

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 4275 - 4314

Published: April 1, 2024

Down syndrome (DS) is a genetic condition where the person born with an extra chromosome 21. DS associated accelerated aging; people are prone to age-related neurological conditions including early-onset Alzheimer's disease. Using Dp(17)3Yey/ + mice, which overexpresses portion of mouse 17, encodes for transsulfuration enzyme cystathionine β-synthase (CBS), we investigated functional role CBS/hydrogen sulfide (H

Language: Английский

Citations

8
Widespread S-persulfidation in activated macrophages as a protective mechanism against oxidative-inflammatory stress DOI Creative Commons

Talal Salti,

Ilana Braunstein,

Yael Haimovich

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103125 - 103125

Published: March 13, 2024

Acute inflammatory responses often involve the production of reactive oxygen and nitrogen species by innate immune cells, particularly macrophages. How activated macrophages protect themselves in face oxidative-inflammatory stress remains a long-standing question. Recent evidence implicates sulfur (RSS) responses; however, how endogenous RSS affect macrophage function response to oxidative insults poorly understood. In this study, we investigated pathways biogenesis clearance macrophages, with particular focus on exploring hydrogen sulfide (H2S)-mediated S-persulfidation influences stress. We show that classical activation mouse or human using lipopolysaccharide interferon-γ (LPS/IFN-γ) triggers substantial H2S/RSS, leading widespread protein persulfidation. Biochemical proteomic analyses revealed surge cellular engaged ∼2% total thiols modified over 800 functionally diverse proteins. was found be largely dependent cystine importer xCT H2S-generating enzyme cystathionine γ-lyase independent changes global proteome. further role sulfide-oxidizing quinone oxidoreductase (SQOR), it acts as negative regulator S-persulfidation. Elevated following LPS/IFN-γ stimulation SQOR inhibition associated increased resistance Upregulation persulfides also inhibited NLRP3 inflammasome provided protection against cell death. Collectively, our findings shed light metabolism effects highlight crucial enabling withstand alleviate

Language: Английский

Citations

5
Metabolic regulation of the host–fungus interaction: from biological principles to therapeutic opportunities DOI Creative Commons
Rita Silva-Gomes, Inês Caldeira, Raquel Fernandes

et al.

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: 116(3), P. 469 - 486

Published: March 18, 2024

Abstract Fungal infections present a significant global public health concern, impacting over 1 billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress recent years, the management of fungal remains challenging. The limited development novel diagnostic therapeutic approaches is largely attributed to our incomplete understanding pathogenetic mechanisms involved these diseases. Recent research has highlighted pivotal role cellular metabolism regulating interaction between fungi their hosts. In response infection, immune cells undergo complex metabolic adjustments meet energy demands necessary for an effective response. A comprehensive circuits governing antifungal immunity, combined with integration individual host traits, holds potential inform medical interventions infections. This review explores insights into immunometabolic regulation host–fungal interactions infection outcome discusses how repurposing cell function could be exploited innovative personalized approaches.

Language: Английский

Citations

5
Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review DOI Open Access
Constantin Munteanu, Daniel Andrei Iordan,

Mihail Hoteteu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15481 - 15481

Published: Oct. 23, 2023

In the rapidly evolving field of Alzheimer's Disease (AD) research, intricate role Hydrogen Sulfide (H

Language: Английский

Citations

11
Analysis of sulfide signaling in rice highlights specific drought responses DOI Creative Commons
Jing Zhang, Ángeles Aroca, Manuel Hervás

et al.

Journal of Experimental Botany, Journal Year: 2024, Volume and Issue: 75(16), P. 5130 - 5145

Published: May 29, 2024

Abstract Hydrogen sulfide regulates essential plant processes, including adaptation responses to stress situations, and the best characterized mechanism of action consists post-translational modification persulfidation. In this study, we reveal first persulfidation proteome described in rice 3443 different persulfidated proteins that participate a broad range biological processes metabolic pathways. addition, comparative proteomics revealed specific involved signaling during drought responses. Several are maintenance cellular redox homeostasis, tricarboxylic acid cycle energy-related pathways, ion transmembrane transport water with aquaporin family showing highest differential levels We activity is regulated by which correlates an increasing level aquaporins. Our findings emphasize impact on total ATP levels, fatty composition, reactive oxygen species, antioxidant enzymatic activities, relative content. Interestingly, role as response differs from current knowledge Arabidopsis, highlights distinct improving tolerance drought.

Language: Английский

Citations

4