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

FEBS Letters

Burk, Raymond F¹  Hill, Kristina E¹  Mostert, Volker¹ 

[1] Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, TN 37232-2279, USA

关键词: Selenium;    Liver;    Heme oxygenase;    Thioredoxin reductase;   

DOI  :  10.1016/S0014-5793(03)00309-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown