Synthesis and secretion of selenoprotein P by cultured rat astrocytes

Selenoprotein P is an extracellular protein that has been postulated to hav e an oxidant defense function. It has survival-promoting properties for cul tured neurons and its mRNA is present in the brain. This study sought to de termine the primary structure of rat brain selenoprotein P and to assess it s production by cultured brain cells. The cDNA of selenoprotein P was isola ted 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 selenoprote in P is the same as selenoprotein P from liver. Astrocytes and a cerebellar granule cell preparation (CGC) were obtained from rat brains and establish ed 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 Se-75-labeled selenite, both cell preparations secreted a Se-75-labele d protein into the medium that corresponded in size to selenoprotein P. Als o, the Se-75-labeled protein could be precipitated from both media with an antiserum to selenoprotein P. This shows that astrocytes and the CGC secret e selenoprotein P. Selenoprotein P is made ill the brain and may have an ox idant defense function there. (C) 2000 Elsevier Science B.V. All rights res erved.