Loss of activity of the selenoenzyme thioredoxin reductase causes induction of hepatic heme oxygenase-1.

Mostert V, Hill KE, Burk RF
FEBS Lett. 2003 541 (1-3): 85-8

PMID: 12706824 · DOI:10.1016/s0014-5793(03)00309-0

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.

MeSH Terms (17)

Animals Aurothioglucose Dinitrochlorobenzene Enzyme Inhibitors Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Liver Male Membrane Proteins Mice Mice, Inbred C57BL Proteins Selenium Selenoprotein P Selenoproteins Thioredoxin-Disulfide Reductase Tumor Cells, Cultured

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