Vitamin E and selenium deficiency induces expression of the ubiquinone-dependent antioxidant system at the plasma membrane

We have used a model of dietary deficiency that leads to a chronic oxidativ e stress to evaluate responses that are adaptations invoked to boost cellul ar defense systems. Long-Evans hooded rats were fed with a diet lacking vit amin E (E) and selenium (Se) for 7 wk from weaning leading to animals defic ient in both nutrients (-E -Se). In the absence of an electron donor, liver plasma membranes from these rats were more sensitive to lipid peroxidation , although they contained 40% greater amounts of ubiquinone than the plasma membranes from rats consuming diets with sufficient vitamin E and Se (+E Se). The incubation of plasma membranes with NAD(P)H resulted in protection against peroxidation, and this effect was more pronounced in -E -Se membra nes. Deficiency was accompanied by a twofold increase in redox activities a ssociated with trans plasma membrane electron transport such as ubiquinone reductase and ascorbate free radical reductase. Staining with a polyclonal antibody against pig liver cytochrome b(5) reductase, which acts as one ubi quinone reductase in the plasma membrane, showed an increased expression of the enzyme in membranes from -E -Se rats. Little DT-diaphorase activity wa s measured in +E +Se plasma membranes, but this activity was dramatically i ncreased in -E -Se plasma membranes. No such increase was found in liver cy tosols, which contained elevated activity of calcium-independent phospholip ase A(2). Thus, ubiquinone-dependent antioxidant protection in +E +Se plasm a membranes is based primarily on NADH-cytochrome bg reductase, whereas add itional protection needed in -E -Se plasma membranes is supported by the in crease of ubiquinone levels, increased expression of the cytochrome br,redu ctase, and translocation of soluble DT-diaphorase to the plasma membrane. O ur results indicate that, in the absence of vitamin E and Se, enhancement o f ubiquinone-dependent reductase systems can fulfill the membrane antioxida nt protection.