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

The glutathione system maintains the thiol redox balance in the mitochondria of fission yeast DOI
Laura de Cubas, Susanna Boronat, Montserrat Rojo de la Vega

et al.

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

Published: April 1, 2025

Language: Английский

Citations

0
Deciphering microbial responses to H2S inhibition of typical functional microorganisms in anaerobic digestion ecosystems DOI Creative Commons

Wenhui Shu,

Bang Du,

Guangxue Wu

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 162766 - 162766

Published: April 1, 2025

Language: Английский

Citations

0
Defective protein persulfidation is involved in obesity associated skeletal muscle dysfunction: role of SIRT-1 DOI Creative Commons
Martina Smimmo,

V. Casale,

D D'Andrea

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 83, P. 103645 - 103645

Published: April 22, 2025

Ectopic fat deposition in skeletal muscle (SKM) due to obesity leads biochemical and morphological alterations that deteriorate SKM quality performance. Here, we show impaired MPST-derived hydrogen sulfide (H2S) signaling contributes obesity-related dysfunction. Muscle tissues from obese db/db mice exhibit reduced MPST expression, correlating with decreased protein persulfidation performance vivo. Mpst-/- similar deficits as mice, confirming the role of MPST. H2S supplementation improves locomotor activity restores persulfidation, including SIRT-1. Myotubes placed an "obese environment" display a downregulation MPST, coupled SIRT-1 leading inflammatory state. Exogenous exerts beneficial effects recovering persulfidation/activity. Finally, biopsies individuals underscoring translational relevance human health. Our study unveils crucial for obesity-associated dysfunction via highlighting importance MPST/H2S pathway maintaining healthy function.

Language: Английский

Citations

0
Computational models as catalysts for investigating redoxin systems DOI
Ché S. Pillay, Johann M. Rohwer

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: 68(1), P. 27 - 39

Published: Feb. 15, 2024

Thioredoxin, glutaredoxin and peroxiredoxin systems play central roles in redox regulation, signaling metabolism cells. In these systems, reducing equivalents from NAD(P)H are transferred by coupled thiol-disulfide exchange reactions to redoxins which then reduce a wide array of targets. However, the characterization redoxin activity has been unclear, with regarded as enzymes some studies metabolites others. Consequently, activities have quantified enzyme kinetic parameters vitro, potentials or ratios within By analyzing all computational models showed that many properties attributed were due system-level effects. Models cellular networks also used estimate intracellular hydrogen peroxide levels, analyze couple omic data understand regulation disease. Computational modeling emerged powerful complementary tool traditional assays integrates number sources into single quantitative framework accelerate analysis systems.

Language: Английский

Citations

3
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

Citations

3