Faculty, Staff and Student Publications
Publication Date
4-19-2023
Journal
International Journal of Molecular Sciences
Abstract
Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; n = 2–4) and organic sulfoxides (GSnOH, n = 1, 2). These reactions reduce NQs and consume oxygen via a semiquinone intermediate. NQs are also reduced as they form adducts with GSH, Cys, protein thiols, and amines. Thiol, but not amine, adducts may increase or decrease H2S oxidation in reactions that are both NQ- and thiol-specific. Amine adducts also inhibit the formation of thiol adducts. These results suggest that NQs may react with endogenous thiols, including GSH, Cys, and protein Cys, and that these adducts may affect both thiol reactions as well as RSS production from H2S.
Keywords
Sulfhydryl Compounds, Thiosulfates, Cysteine, Hydrogen Sulfide, Oxidation-Reduction, Glutathione, Proteins, Oxygen, Naphthoquinones, reactive sulfur species, reactive oxygen species, antioxidants, naphthoquinones, naphthoquinone thiol adducts
DOI
10.3390/ijms24087516
PMID
37108682
PMCID
PMC10138938
PubMedCentral® Posted Date
4-19-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes