Selective induction of liver parenchymal cell heme oxygenase-1 in selenium-deficient rats

被引：19

作者：

Mostert, V

Hill, KE

Ferris, CD

Burk, RF ^{[1
]}

机构：

[1] Vanderbilt Univ, Dept Med, Sch Med, Div Gastroenterol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, Clin Nutr Res Unit, Nashville, TN 37232 USA

来源：

BIOLOGICAL CHEMISTRY | 2003年 / 384卷 / 04期

关键词：

AP-1; heme oxygenase; hepatocytes; induction; liver; selenium;

D O I：

10.1515/BC.2003.076

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Liver heme oxygenase (HO) activity is higher in selenium-deficient rats than in control animals under basal conditions and is further increased in them, but not in controls, by phenobarbital treatment. In the present study we characterized liver HO induction by selenium deficiency using molecular methods. Severe selenium deficiency in rats caused a doubling of liver HO activity without affecting spleen, kidney, brain, or testis HO activities. HO-1 protein and mRNA were increased to accompany the increased HO activity, but HO-2 protein and mRNA were not increased. Fractionation of the liver into hepatocyte and Kupffer cell/endothelial cell fractions revealed that the increased HO activity resides in the hepatocyte fraction. Immunohistochemical localization of HO-1 protein confirms the induction of HO-1 taking place solely in hepatocytes and throughout the liver lobule. Phenobarbital treatment sharply increased HO-1 mRNA and protein expression in selenium-deficient liver and HO activity in hepatocytes, but had no effect in control liver or in the Kupffer cell/endothelial cell fraction of selenium-deficient liver. Electrophoretic mobility shift assays showed increased AP-1 binding activity, suggesting an involvement of this redox-sensitive transcription factor in the induction by phenobarbital of HO-1 in selenium deficiency. We speculate that selenium deficiency affects hepatic antioxidant selenoproteins, resulting in an up-regulation of HO-1.

引用

页码：681 / 687

页数：7

共 31 条

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