Synthesis and secretion of selenoprotein P by cultured rat astrocytes

Selenoprotein P is an extracellular protein that has been postulated to have an oxidant defense function. It has survival-promoting properties for cultured neurons and its mRNA is present in the brain. This study sought to determine the primary structure of rat brain selenoprotein P and to assess its production by cultured brain cells. The cDNA of selenoprotein P was isolated from a rat brain cDNA library and was found to encode the same peptide sequence as rat liver cDNA. Thus the primary structure of brain selenoprotein P is the same as selenoprotein P from liver. Astrocytes and a cerebellar granule cell preparation (CGC) were obtained from rat brains and established in culture. The CGC was estimated to contain up to 5% glial cells. Both preparations were shown to contain selenoprotein P mRNA. During incubation with (75)Se-labeled selenite, both cell preparations secreted a (75)Se-labeled protein into the medium that corresponded in size to selenoprotein P. Also, the (75)Se-labeled protein could be precipitated from both media with an antiserum to selenoprotein P. This shows that astrocytes and the CGC secrete selenoprotein P. Selenoprotein P is made in the brain and may have an oxidant defense function there.