Biomedical subjects

Raymond F Burk

Publications and source records attributed to Raymond F Burk.

22 records · Page 2Linked to original sources

PubMed2003

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.

Animals↗

PubMed2002

Thioredoxin reductase reduces lipid hydroperoxides and spares alpha-tocopherol.

We investigated whether and how rat liver thioredoxin reductase spares alpha-tocopherol in biomembranes. Purified hydroperoxides of beta-linoleoyl-gamma-palmitoylphosphatidylcholine were decreased 35% by treatment with thioredoxin reductase and 54% by thioredoxin reductase plus E. coli thioredoxin. Thioredoxin reductase also halved the amount of hydroperoxides that had been formed during photoperoxidation of liposomes composed of beta-linoleoyl-gamma-palmitoylphosphatidylcholine, and of emulsions of both cholesterol and cholesteryl linolenate. In erythrocyte ghosts, thioredoxin reductase spared alpha-tocopherol from oxidation by both soybean lipoxygenase and ferricyanide. Thioredoxin reductase also decreased F(2)-isoprostanes in ghosts oxidized by ferricyanide, suggesting that its ability to spare alpha-tocopherol relates to reduction of lipid hydroperoxides.

Animals↗

PubMed2002

Mass spectrometric characterization of full-length rat selenoprotein P and three isoforms shortened at the C terminus. Evidence that three UGA codons in the mRNA open reading frame have alternative functions of specifying selenocysteine insertion or translation termination.

Selenoprotein P is an abundant extracellular glycoprotein. Its mRNA contains 10 UGAs in an open reading frame terminated by a UAA. This predicts that full-length selenoprotein P will contain 10 selenocysteine residues. Full-length selenoprotein P and three smaller isoforms that have identical N termini have been demonstrated. Selenoprotein P was purified from rat plasma, and the four isoforms were separated by heparin chromatography and SDS-PAGE. Mass spectrometric peptide analysis of the full-length isoform verified 357 of its 366 predicted amino acid residues, including its C terminus and all 10 selenocysteines. The C termini of the smaller isoforms were characterized by mass spectrometry. The shortened isoforms terminated where the second, third, and seventh selenocysteine residues were predicted to be. This suggests that all isoforms arise from the same mRNA and that the UGAs that specify the second, third, and seventh selenocysteines in full-length selenoprotein P can alternatively serve to terminate translation, producing the shorter isoforms.

Amino Acid Sequence↗

PubMedDate not supplied

Selenium, an antioxidant nutrient.

Selenium is an essential constituent of a number of enzymes, some of which have antioxidant functions. Deficiency of the element in animals makes them susceptible to injury by certain types of oxidative stress. At least 1 human disease occurs only in selenium-deficient individuals. Therefore, it seems prudent to avoid selenium deficiency. The plasma (or serum) selenium concentration is often used to assess selenium nutritional status. A plasma selenium concentration of 8 micrograms/dL or greater in a healthy subject indicates that plasma selenoproteins are optimized and the subject is selenium replete. The Third National Health and Nutrition Examination Survey determined plasma selenium in 17,630 subjects in the United States. Its results indicate that more than 99% of the subjects studied were selenium replete. The Institute of Medicine has set the Recommended Dietary Allowance for selenium at 55 micrograms per day for adults. Since most estimates of selenium intake in the United States are 80 micrograms per day or greater, routine selenium supplementation is not recommended in the United States.

Antioxidants↗