title: Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation.
abstract: For decades, reactive persulfide species including cysteine persulfide (CysSSH) have been known to exist endogenously in organisms. However, the physiological significance of endogenous persulfides remains poorly understood. That cystathionine β-synthase and cystathionine γ-lyase produced CysSSH from cystine was recently demonstrated. An endogenous sulfur transfer system involving CysSSH evidently generates glutathione persulfide (GSSH) that exists at concentrations greater than 100 μM in vivo. Because reactive persulfide species such as CysSSH and GSSH have higher nucleophilicity than parental cysteine (Cys) and glutathione do, these reactive species exhibit strong scavenging activities against oxidants, e.g., hydrogen peroxide, and electrophiles, which contributes to redox signaling regulation. Also, several papers indicated that various proteins and enzymes have Cys polysulfides including CysSSH at their specific Cys residues, which is called protein polysulfidation. Apart from the redox signaling regulatory mechanism, another plausible function of protein polysulfidation is providing protection for protein thiol residues against irreversible chemical modification caused by oxidants and electrophiles. Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases.
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. shingok@med.tohoku.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kasamatsu
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Akira.Nishimura@med.tohoku.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. morita@med.tohoku.ac.jp.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. matsunag@med.tohoku.ac.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. hisyamabdulhamid@gmail.com.
authors.forename: Hisyam
authors.initials: H
authors.lastname: Abdul Hamid
authors.affiliation: Department of Environmental Health Science and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. takaike@tohoku.med.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
mesh_terms: D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D010084:Oxidation-Reduction / Q000187:drug effects; D015398:Signal Transduction; D013481:Superoxides / Q000737:chemistry*
chemical_list: D004220:Disulfides; C000611742:glutathione persulfide; D013481:Superoxides; C116840:cysteine persulfide; D006861:Hydrogen Peroxide; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003545:Cysteine
keywords: protein polysulfidation; reactive persulfide species; redox signaling; thiol modification