Abstract
Cholesterol esters are relatively abundant during early brain development and essentially disappear after myelination. However little is known about the role of cholesterol esters and the regulation of their synthesis. In this study regulation of cholesterol ester and cholesterol syntheses by desmosterol was studied in C-6 glial cells, a model of the glial cell found just prior to myelination. Cholesterol ester synthesis (from [14C]oleate) was stimulated as much as 12-fold after just 5 hours' exposure to desmosterol. Cholesterol synthesis (from [14C]acetate) was inhibited in a simultaneous and quantitatively similar manner. Observation of similar effects on the syntheses of cholesterol ester and cholesterol from 3H2O indicated that alterations in pool sizes of intermediates did not contribute to the observed responses. Experiments utilizing prelabeled intracellular cholesterol suggested that desmosterol produced its effect by stimulating esterification of primarily endogenous cholesterol. Thus, regulation of cholesterol ester synthesis is active and tightly linked to regulation of cholesterol synthesis in this model of the premyelinating glial cell. The data suggest that prior to myelination desmosterol stimulates cholesterol ester synthesis and inhibits cholesterol synthesis. When the demand for glial cholesterol becomes great, i.e. with rapid myelination, desmosterol is converted to cholesterol, cholesterol ester synthesis is inhibited, and cholesterol synthesis is disinhibited.
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Volpe, J. 1160 THE RELATION OF CHOLESTEROL ESTER & CHOLESTEROL SYNTHESES TO THE INITIATION OF MYELINATION. Pediatr Res 12 (Suppl 4), 557 (1978). https://doi.org/10.1203/00006450-197804001-01166
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DOI: https://doi.org/10.1203/00006450-197804001-01166
