Loss of activity of the selenoenzyme thioredoxin reductase causes induction of hepatic heme oxygenase-1.
The stress response enzyme heme oxygenase (HO)-1 is induced in livers of selenium-deficient rodents, probably to compensate for loss of certain selenoproteins. We sought to identify those selenoproteins. Selenium-replete mice with genetic deletion of selenoprotein P or glutathione peroxidase-1 did not have elevated hepatic HO activity, thus ruling out involvement of those selenoproteins in HO-1 induction by selenium deficiency. However, inhibition of thioredoxin reductase (TrxR) by a low dose of gold in the form of aurothioglucose led to induction of hepatic HO activity. Moreover, further induction by phenobarbital was observed. This HO-1 induction pattern is also seen in selenium-deficient mice. In the rat hepatoma cell line H4IIE, inhibition of TrxR by aurothioglucose or by 1-chloro-2,4-dinitrobenzene led to induction of HO-1. We conclude that loss of TrxR is responsible for the induction of HO-1 by selenium deficiency.
Mostert
Volker
V
Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, TN 37232-2279, USA.
Hill
Kristina E
KE
Burk
Raymond F
RF
D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000378:metabolism; D051547:Heme Oxygenase-1; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000378:metabolism*; D012643:Selenium / Q000172:deficiency*; D051149:Selenoprotein P; D051140:Selenoproteins; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004137:Dinitrochlorobenzene; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D006051:Aurothioglucose; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013880:Thioredoxin-Disulfide Reductase; D012643:Selenium