title: Effect of selenite on T-cell mitogenesis: contribution of ROS production and apoptosis signal-regulating kinase 1.
abstract: Although supplementation with the selenocompound, sodium selenite has been shown to stimulate the concanavalin A-induced T-cell mitogenic response, the mechanisms responsible remain unclear. This study was conducted to evaluate the relationships between the induction of apoptosis, formation of tumor necrosis factor (TNF)-alpha and reactive oxygen species (ROS), activation of apoptosis signal-regulating kinase (ASK) 1 and the thioredoxin (Trx) system when mitogenesis was stimulated by selenite. TNF-alpha was dose-dependently released by mouse splenocytes treated with selenite, and apoptosis was induced when TNF-alpha was added at the indicated concentrations. However, supplementation with selenite at low concentrations inhibited the accumulation of ROS with the increased expression of Trx reductase 1 and induction of apoptosis in wild-type splenocytes, and also at high concentrations in Trx-1-transgenic mouse splenocytes. The suppression of apoptosis was accompanied by a decrease in the expression of phospho-ASK1. These results suggest that the stimulation of T-cell mitogenesis by selenite may be partly attributed to the inhibited accumulation of ROS due to a reduced Trx-1/TR1 system, the inactivation of ASK1, and the suppression of apoptosis.
authors.affiliation: Department of Public Health & Preventive Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kajihara
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Okuno
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Sakazaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arakawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ogino
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nakamuro
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020887:Selenious Acid / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008934:Mitogens; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D013879:Thioredoxins; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D020887:Selenious Acid