Secretion of Sterols and the NPC2 Protein from Primary Astrocytes
Open accessAbstract
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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Cholesterol and desmosterol play essential roles during embryogenesis, myelination, and brain development.
“cholesterol and desmosterol play essential roles during embryogenesis, myelination, and brain development [2–4].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [4]
The Abstract says most brain sterol is acquired during early-development myelination, and the Discussion reports desmosterol in developing brain and embryonic astrocytes. These passages connect the sterols to development and myelination, but do not establish that both play essential roles in embryogenesis, myelination, and brain development. (LLM, conf=0.85)
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- Authors
- Mutka, A.-L., Lusa, S., Linder, M. D., Jokitalo, E., Kopra, O., Jauhiainen, M., & Ikonen, E.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Ikonen, Elina
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 279
- Issue
- 47
- Pages
- 48654-48662
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2151302138
- Cited by
- 56
- References
- 45
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 2 · 2013: 1 · 2012: 3
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- astrocytes, NPC1, Niemann-Pick disease type C, cholesterol, desmosterol, lathosterol, sterol biosynthesis, lipoprotein particles, cholesterol precursors
- MeSH terms
- Niemann-Pick C1 Protein, Animals, Astrocytes, Carrier Proteins, Cells, Cultured, Centrifugation, Density Gradient, Cholesterol, Chromatography, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Fibroblasts, Genotype, Glycoproteins, Glycoside Hydrolases, Glycosylation, Humans, Mice, Inbred BALB C, Mice, Transgenic, Microscopy, Electron, Microscopy, Fluorescence, Proteins, Semliki forest virus, Sterols, Sucrose, Temperature, Time Factors, Blotting, Western, DNA, Complementary, Vesicular Transport Proteins, Intracellular Signaling Peptides and Proteins, Mice
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