Effect of mercury on selenium utilization and selenoperoxidase activity in LNCaP cells.
Formation of stable complexes with protein thiols is the best-known mechanism of mercury toxicity. However, the solubility product of Hg(2+) with sulfides, although very low, is higher than that with selenides, suggesting that the fully reduced form of selenium might also be a relevant target for Hg(2+). In cells, selenide is the suggested intermediate for selenoprotein biosynthesis and selenoenzymes, in turn, contain reduced selenium as the catalytic moiety. Thus, inhibition of biological functions of selenium could be seen as a different mechanism of Hg(2+) toxicity. To address this issue, we investigated selenoperoxidase (SeGPx) activity in LNCaP cells exposed to HgCl(2). Cells growing in standard medium express a low GPx activity, which increases on addition of selenium donors such as selenite, selenomethionine, or methyl-Se-cysteine. HgCl(2) added to the medium has different effects depending on the type of Se donor. A progressive decrease of SeGPx activity is observed in cells grown in standard medium exposed to HgCl(2), while coadministration of suprastoichiometric amounts of HgCl(2) prevents the increase of SeGPx activity only when selenite, but not selenomethionine or methyl-Se-cysteine, is the selenium source. From this evidence we conclude that HgCl(2): (a) does not inhibit directly SeGPxs, as confirmed on isolated enzymes; (b) does not interfere with the intermediates of the metabolic pathway of selenoprotein synthesis; and (c) decreases the bioavailability of selenium only when ionic complexes can be formed.
Bulato
Cristiana
C
Department of Biological Chemistry, Viale G. Colombo 3, I-35121 Padova, Italy.
Bosello
Valentina
V
Ursini
Fulvio
F
Maiorino
Matilde
M
D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000633:toxicity*; D011471:Prostatic Neoplasms; D012643:Selenium / Q000378:metabolism*; D017279:Selenocysteine / Q000378:metabolism; D012645:Selenomethionine / Q000378:metabolism; D051140:Selenoproteins / Q000378:metabolism*; D018038:Sodium Selenite / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D051140:Selenoproteins; D017279:Selenocysteine; D012645:Selenomethionine; D006861:Hydrogen Peroxide; D008628:Mercury; D012643:Selenium; D018038:Sodium Selenite