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Publication : Secretion of sterols and the NPC2 protein from primary astrocytes.

First Author  Mutka AL Year  2004
Journal  J Biol Chem Volume  279
Issue  47 Pages  48654-62
PubMed ID  15355983 Mgi Jnum  J:95002
Mgi Id  MGI:3522418 Doi  10.1074/jbc.M405345200
Citation  Mutka AL, et al. (2004) Secretion of sterols and the NPC2 protein from primary astrocytes. J Biol Chem 279(47):48654-62
abstractText  Astrocytes secrete cholesterol in lipoprotein particles. Here we show that primary murine embryonic astrocytes secrete endogenously synthesized cholesterol but also the cholesterol precursors desmosterol and lathosterol. In astrocyte membranes, desmosterol and cholesterol were the predominant sterols. Astrocytes derived from Niemann-Pick type C lipidosis (NPC1-/-) mice displayed late endosomal cholesterol deposits, but the secretion of biosynthetic sterols from the cells was not inhibited. Both wild-type and NPC1-/- astrocytes secreted the NPC2 protein. Size-exclusion chromatography combined with electron microscopy showed that the majority of sterols were secreted separately from NPC2 in heterogeneous spherical particles with an average diameter of 20 nm. These data suggest that NPC2 and the majority of sterols secreted from astrocytes are not released together and that the secretion of neither sterols nor NPC2 requires NPC1 function. In addition, the findings reveal a complexity of sterol species in astrocytes and bring up the possibility that some of the effects assigned to astrocyte cholesterol may be attributed to its penultimate precursors.
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