507-29-9Relevant articles and documents
An uncommon redox behavior sheds light on the cellular antioxidant properties of ergothioneine
Servillo, Luigi,Castaldo, Domenico,Casale, Rosario,D'Onofrio, Nunzia,Giovane, Alfonso,Cautela, Domenico,Balestrieri, Maria Luisa
, p. 228 - 236 (2015)
Ergothioneine (ESH), an aromatic thiol occurring in the human diet and which accumulates in particular cells, is believed to act as an antioxidant. However, its redox mechanism remains unclear and it does not seem to provide any advantage compared to other antioxidants, such as alkylthiols, which are better reducing agents and generally present in cells at higher levels. Here, we investigated by ESI-MS the products of ESH oxidation produced by neutrophils during oxidative burst and, to further elucidate ESH redox behavior, we also analyzed the oxidation products of the reaction of ESH with hypochlorite in cellfree solutions. Indeed, neutrophils are the main source of hypochlorite in humans. Furthermore, we also tested other biologically relevant oxidants, such as peroxynitrite and hydrogen peroxide. Our results indicate that treatment of human neutrophils with phorbol 12-myristate 13-acetate in the presence of ESH leads to a remarkable production of the sulfonated form (ESO3H), a compound never described before, and hercynine (EH), the desulfurated form of ESH. Similar results were obtained when ESH was subjected to cell-free oxidation in the presence of hypochlorite, as well as hydrogen peroxide or peroxynitrite. Furthermore, when the disulfide of ESH was reacted with those oxidants, we found that it was also oxidized, with production of EH and ESO3H, whose amount was dependent on the oxidant strength. These data reveal a unique ESH redox behavior, entirely different from that of alkylthiols, and suggest a mechanism, so far overlooked, through which ESH performs its antioxidant action in cells.
Probing the substrate specificity of the ergothioneine transporter with methimazole, hercynine, and organic cations
Grigat, Silke,Harlfinger, Stephanie,Pal, Sonia,Striebinger, Ralph,Golz, Stefan,Geerts, Andreas,Lazar, Andreas,Schoemig, Edgar,Gruendemann, Dirk
, p. 309 - 316 (2007)
Recently, we have identified the ergothioneine (ET) transporter ETT (gene symbol SLC22A4). Much interest in human ETT has been generated by case-control studies that suggest an association of polymorphisms in the SLC22A4 gene with susceptibility to chronic inflammatory diseases. ETT was originally designated a multispecific novel organic cation transporter (OCTN1). Here we reinvestigated, based on stably transfected 293 cells and with ET as reference substrate, uptake of quinidine, verapamil, and pyrilamine. ETT from human robustly catalyzed transport of ET (68 μl/(min mg protein)), but no transport of organic cations was discernible. With ET as substrate, ETT was relatively resistant to inhibition by selected drugs; the most potent inhibitor was verapamil (Ki = 11 μmol/l). The natural compound hercynine and antithyroid drug methimazole are related in structure to ET. However, efficiency of ETT-mediated transport of methimazole (Ki = 7.5 mmol/l) was 130-fold lower, and transport of hercynine (Ki = 1.4 mmol/l) was 25-fold lower than transport of ET. ETT from mouse, upon expression in 293 cells, catalyzed high affinity, sodium-driven uptake of ET very similar to ETT from human. Additional real-time PCR experiments based on 16 human tissues revealed ETT mRNA levels considerably lower than in bone marrow. Our experiments establish that ETT is highly specific for its physiological substrate ergothioneine. ETT is not a cationic drug transporter, and it does not have high affinity for organic cation inhibitors. Detection of ETT mRNA or protein can therefore be utilized as a specific molecular marker of intracellular ET activity.
Synthesis of N-methyl urocanates of hydroxyderivatives of isocembrol
Valeev,Salikhov,Krasnoslobodtseva,Sharipov,Spirikhin,Tolstikov
, p. 143 - 148 (2008/03/11)
Alcohols were prepared by stereospecific hydroxylation of isocembrol and were esterified into N-methylurocanates, proposed biomimetics of taxol.
