title: Ergothioneine products derived by superoxide oxidation in endothelial cells exposed to high-glucose.
abstract: Ergothioneine (Egt), 2-mercapto-L-histidine betaine (ESH), is a dietary component acting as antioxidant and cytoprotectant. In vitro studies demonstrated that Egt, a powerful scavenger of hydroxyl radicals, superoxide anion, hypochlorous acid and peroxynitrite, protects vascular function against oxidative damages, thus preventing endothelial dysfunction. In order to delve the peculiar oxidative behavior of Egt, firstly identified in cell free-systems, experiments were designed to identify the Egt oxidation products when endothelial cells (EC) benefit of its protection against high-glucose (hGluc). HPLC-ESI-MS/MS analyses revealed a decrease in the intracellular GSH levels and an increase in the ophthalmic acid (OPH) levels during hGluc treatment. Interestingly, in the presence of Egt, the decrease of the GSH levels was lower than in cells treated with hGluc alone, and this effect was paralleled by lower OPH levels. Egt was also effective in reducing the cytotoxicity of H2O2and paraquat (PQT), an inducer of superoxide anion production, showing a similar time-dependent pattern of GSH and OPH levels, although with peaks occurring at different times. Importantly, Egt oxidation generated not only hercynine (EH) but also the sulfonic acid derivative (ESO3H) whose amounts were dependent on the oxidative stress employed. Furthermore, cell-free experiments confirmed the formation of both EH and ESO3H when Egt was reacted with superoxide anion. In summary, these data, by identifying the EH and ESO3H formation in EC exposed to hGluc, highlight the cellular antioxidant properties of Egt, whose peculiar redox behavior makes it an attractive candidate for the prevention of oxidative stress-associated endothelial dysfunction during hyperglycemia.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Servillo
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: D'Onofrio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Casale
authors.affiliation: Stazione Sperimentale per le Industrie delle Essenze e dei derivati dagli Agrumi, Azienda Speciale della Camera di Commercio di Reggio Calabria, Reggio Calabria, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Cautela
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Giovane
authors.affiliation: Stazione Sperimentale per le Industrie delle Essenze e dei derivati dagli Agrumi, Azienda Speciale della Camera di Commercio di Reggio Calabria, Reggio Calabria, Italy; Ministero dello Sviluppo Economico, MiSE, Roma, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Castaldo
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: marialuisa.balestrieri@unicampania.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Balestrieri
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001622:Betaine / Q000031:analogs & derivatives / Q000378:metabolism; D002417:Cattle; D016923:Cell Death; D002474:Cell-Free System; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology*; D004880:Ergothioneine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006639:Histidine / Q000031:analogs & derivatives / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013451:Sulfonic Acids / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; D013451:Sulfonic Acids; D013481:Superoxides; C016632:ophthalmic acid; D001622:Betaine; D006639:Histidine; D006861:Hydrogen Peroxide; D004880:Ergothioneine; D005978:Glutathione; D005947:Glucose; C007928:hercynine
keywords: Endothelial cells; Ergothioneine; Ergothioneine sulfonic acid; Hyperglycaemia; Ophthalmic acid; Superoxide anion