Knockout of cellular glutathione peroxidase affects selenium-dependent parameters similarly in mice fed adequate and excessive dietary selenium.
This study was to determine whether or not effects of the cellular glutathione peroxidase (GPX1) knockout on several Se-dependent parameters in mice were tissue, dietary Se concentration, and selenoprotein specific. A 2 x 3 factorial experiment was conducted with 18 GPX1 knockout mice [GPX1(-)] and 18 controls (3 weeks old, half males and females). These mice were fed a torula yeast diet supplemented with all-rac-alpha-tocopheryl acetate (50 mg/kg of feed) and Se (sodium selenite) at 0, 0.5, or 3.0 mg/kg of feed for 6 weeks. Both kidney GPX1 mRNA levels and liver, kidney, lung, and testis total GPX activities, assayed using hydrogen peroxide, were affected (p < 0.001) by the GPX1 knockout and dietary Se concentrations, whereas kidney extracellular or plasma GPX (GPX3) mRNA levels and phospholipid hydroperoxide GPX (GPX4) activities in the four tissues were affected (p < 0.001) by only dietary Se concentrations. Total GPX activity in testis was reduced approximately 90% (p < 0.01) by the GPX1 knockout. Neither the GPX1 knockout nor the dietary Se concentrations affected mRNA levels of GPX4 in testis or selenoprotein P in kidney. Total liver Se concentrations were not different between the GPX1(-) and control mice at 0 mg Se/kg of feed, but were reduced (p < 0.01) by 61 and 64% in the GPX1(-) mice at 0.5 and 3.0 mg Se/kg of feed, respectively. These results not only confirm the independent expression of GPX3, GPX4, and selenoprotein P from that of GPX1, but also show similar effects of the GPX1 knockout on Se-dependent parameters in mice between different dietary Se concentrations, tissues, and selenoproteins.
Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
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D000818:Animals; D004032:Diet; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012643:Selenium / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D051149:Selenoprotein P; D051140:Selenoproteins; D013737:Testis / Q000201:enzymology
D007527:Isoenzymes; D011506:Proteins; D012333:RNA, Messenger; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium