Selenoprotein P. Nutritional and clinical aspects

Abstract: In this thesis, the nutritional regulation and clinical significance of selenoprotein P (SeP) in human plasma of healthy and diseased subjects was investigated. For the analysis of SeP, a radioimmunoassay was developed using polyclonal antibodies. The epitope recognized by the antibodies was apparently stable after storage of plasma in the frozen state for years. In the studies included, the coefficient of variation for the concentration of SeP was 3.8-7.7% within assays, and 5.4-7.5% between assays. The levels of SeP among healthy adults from different parts of Europe varied significantly. When the highest concentration of SeP encountered in samples from Maldegem (Belgium) was set to 100%, the mean concentration for the lowest region was 69% for Epirus (Greece). These differences would largely be expected to reflect differences in selenium intake. In two similar trials, healthy Finnish males were daily receiving oral supplements as inorganic or organic selenium during 11 to 16 weeks. At a low selenium status the SeP levels of all the supplemented groups increased in a similar way, approaching a plateau at 2 weeks, and reaching maximum values at 4 weeks. At a higher selenium status no significant effects on SeP levels were observed. In another study it was investigated if SeP in plasma is lost during treatment of hypercholesterolaemic patients with LDL-apheresis. Immediately after LDL-apheresis a substantial decrease of SeP in the plasma was observed. These results indicate that the decrease of plasma selenium during treatment was due to the binding of SeP to the dextran sulphate cellulose column to a large extent. The SeP lost during one treatment would correspond to 90 µg selenium. In a case-control study, the premorbid levels of SeP in the plasma of middle-aged men who later got different forms of cancer was compared with those of control subjects. Low SeP levels were associated with an increased risk of getting cancer in respiratory tract and digestive tract. In all study groups, the correlations of SeP to plasma selenium and eGSHPx was positive, usually being more marked att low to moderate plasma selenium concentrations. SeP is evidently ubiquitously expressed and is associated with endotelial cells. Its localization is consistent with the assumption that it has an oxidant defense function. The marked variation in SeP levels observed in the present series of investigations may have several medical implications.