title: Sterol synthesis by myelinating cultures of mouse spinal cord.
abstract: We studied the control of sterol synthesis during myelination of central nervous system in culture. Explants of fetal mouse spinal cord were cultured for 3-30 days in vitro (DIV). Myelination was visible by electron micriscopy at 3 DIV, and by bright-field light microscopy beginning at 6 DIV. All explants were heavily myelinated by 15 DIV. Specific activity of 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) increased rapidly until 15 DIV. The rate of incorporation of [1-14C]acetate into sterol was greatest at 12 DIV, more than double that at 4 and 22 DIV. Specific activity of the mevalonate synthesizing enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) was greatest at 11 DIV, threefold greater than at 6 and 30 DIV. Previous studies in fibroblasts and other non-neural tissues had shown that deprivation of exogenous lipid caused a rapid increase in HMG CoA reductase activity. In contrast, when the spinal cord explants were incubated for 24 h in a lipid-deficient medium, there was either a marked decrease in specific activity of HMG CoA reductase (at 6, 15 and 30 DIV), or no change in enzyme activity (at 11 DIV).
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000085:Acetates / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D003897:Desmosterol / Q000096:biosynthesis; D005333:Fetus; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D066298:In Vitro Techniques; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D009186:Myelin Sheath / Q000648:ultrastructure; D013261:Sterols / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D000085:Acetates; D008055:Lipids; D013261:Sterols; D003897:Desmosterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases