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- Title
Loss of activity of the selenoenzyme thioredoxin reductase causes induction of hepatic heme oxygenase-1
- Authors
Mostert, Volker; Hill, Kristina E.; Burk, Raymond F.
- Abstract
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.
- Subjects
SELENIUM; LIVER
- Publication
FEBS Letters, 2003, Vol 541, Issue 1-3, p85
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(03)00309-0