title: Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells.
abstract: Maintaining a redox balance by means of precisely controlled systems that regulate production, and elimination, and metabolism of electrophilic substances (electrophiles) is essential for normal cardiovascular function. Electrophilic signaling is mainly regulated by endogenous electrophiles that are generated from reactive oxygen species, nitric oxide, and the derivative reactive species of nitric oxide during stress responses, as well as by exogenous electrophiles including compounds in foods and environmental pollutants. Among electrophiles formed endogenously, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) has unique cell signaling functions, and pathways for its biosynthesis, signaling mechanism, and metabolism in cells have been clarified. Reactive persulfide species such as cysteine persulfides and polysulfides that are endogenously produced in cells are likely to be involved in 8-nitro-cGMP metabolism. These new aspects of redox biology may stimulate innovative and multidisciplinary research in cardiovascular physiology and pathophysiology. In our review, we focus on the redox-dependent regulation of electrophilic signaling via reduction and metabolism of electrophiles by reactive persulfides in cardiac cells, and we include suggestions for a new therapeutic strategy for cardiovascular disease.
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan; Department of Translational Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; PRESTO, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan. Electronic address: nishida@nips.ac.jp.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishida
authors.affiliation: Division of Cardiocirculatory Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (School of Life Science, The Graduate University for Advanced Studies), Okazaki 444-8787, Japan.
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kasamatsu
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: takaike@med.tohoku.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013440:Sulfides / Q000378:metabolism
chemical_list: C525106:8-nitroguanosine 3',5'-cyclic monophosphate; D004220:Disulfides; D017382:Reactive Oxygen Species; D013440:Sulfides; D009569:Nitric Oxide; C116840:cysteine persulfide; C032915:polysulfide; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D003545:Cysteine
keywords: 8-Nitro-cGMP; Electrophilic signaling; Reactive persulfide species; Reductive stress; Senescence