title: The chemical biology of protein hydropersulfides: Studies of a possible protective function of biological hydropersulfide generation.
abstract: The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins.
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Millikin
authors.affiliation: Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bianco
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Corey
authors.initials: C
authors.lastname: White
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Simran S
authors.initials: SS
authors.lastname: Saund
authors.affiliation: Department of Biology, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Henriquez
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Sosa
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.affiliation: Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Soeda
authors.affiliation: Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Toscano
authors.affiliation: Department of Biology, Sonoma State University, Rohnert Park, CA 94928, United States. Electronic address: linj@sonoma.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Chemistry, Sonoma State University, Rohnert Park, CA 94928, United States. Electronic address: fukuto@sonoma.edu.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Fukuto
mesh_terms: D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013440:Sulfides; C051552:persulfides; D003545:Cysteine
keywords: Cellular protection; Electrophilic stress; Hydrogen sulfide; Hydropersulfides; Oxidative stress; Thiol protein; Thiols