Organoselenium compounds modulate extracellular redox by induction of extracellular cysteine and cell surface thioredoxin reductase.
The effect of selenium compounds on extracellular redox modulating capacity was studied in murine macrophage RAW 264.7 cells and differentiated human THP-1 monocytes. The arylselenium compounds benzeneselenol (PhSeH), dibenzyl diselenide (DBDSe), diphenyl diselenide (DPDSe), and ebselen were capable of inducing extracellular cysteine accumulation via a cystine- and glucose-dependent process. Extracellular cysteine production was dose-dependently inhibited by glutamate, an inhibitor of cystine/glutamate antiporter (Xc(-) transporter), supporting the involvement of Xc(-) transporter for cystine uptake in the above process. These arylselenium compounds also induced cellular thioredoxin reductase (TrxR) expression, particularly at the exofacial surface of cells. TrxR1 knockdown using small interfering RNA attenuated TrxR increases and cysteine efflux induced in cells by DPDSe. Sodium selenite (Na2SeO3), selenomethionine (SeMet), seleno-l-cystine (SeCySS), and Se-methylselenocysteine (MeSeCys) did not have these effects on macrophages under the same treatment conditions. The effects of organoselenium compounds on extracellular redox may contribute to the known, but inadequately understood, biological effects of selenium compounds.
Department of Food Science, University of Wisconsin, 1605 Linden Drive, Madison, WI 53706, United States. gdzhang@ucdavis.edu
Guodong
G
Zhang
Viriya
V
Nitteranon
Shanshan
S
Guo
Peiju
P
Qiu
Xian
X
Wu
Feng
F
Li
Hang
H
Xiao
Qiuhui
Q
Hu
Kirk L
KL
Parkin
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D013880:Thioredoxin-Disulfide Reductase / Q000032:analysis / Q000378:metabolism*
D016566:Organoselenium Compounds; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine