Selective induction of liver parenchymal cell heme oxygenase-1 in selenium-deficient rats.
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.
Division of Gastroenterology, Department of Medicine and Clinical Nutrition Research Unit, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Volker
V
Mostert
Kristina E
KE
Hill
Christopher D
CD
Ferris
Raymond F
RF
Burk
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000201:enzymology; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D022781:Hepatocytes / Q000201:enzymology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000172:deficiency*; D014018:Tissue Distribution
D007527:Isoenzymes; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D012643:Selenium; D010634:Phenobarbital