title: Glutathione contributes to the efflux of selenium from hepatoma cells.
abstract: Selenite is a selenium source for selenoprotein biosynthesis in mammalian cells. Although previous studies have suggested the involvement of glutathione (GSH) and/or thioredoxin reductase in selenite metabolism, intracellular selenite metabolism remains largely unknown. Here, we report that GSH depletion did not affect the amount of selenoprotein in Hepa 1-6 cells, suggesting that GSH does not play a central role in the reduction of selenite in selenoprotein biosynthesis. On the other hand, we found that GSH is involved in the efflux of low-molecular-weight selenium compounds from cells, presumably via the formation of selenodiglutathione. Moreover, selenite inhibited the efflux of a fluorescent bimane-GS conjugate that is mediated by ATP-dependent multidrug-resistant proteins, implying the existence of an active transporter for selenodiglutathione. This is the first report demonstrating that GSH plays a role in selenium excretion from cells by forming a GSH-conjugate, which may contribute to the distribution, detoxification, and homeostasis of selenium in the body.
authors.affiliation: a Institute for Chemical Research , Kyoto University , Kyoto , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kurihara
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Esaki
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Mihara
mesh_terms: D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000096:biosynthesis
chemical_list: D026901:Membrane Transport Proteins; D051140:Selenoproteins; D005978:Glutathione; D012643:Selenium
keywords: glutathione; selenite; selenium efflux; selenodiglutathione; selenoprotein