Hormonal Regulation of the mRNA Encoding the Ketogenic Enzyme Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase in Neonatal Primary Cultures of Cortical Astrocytes and Meningeal Fibroblasts |
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Authors: | Tim E. Cullingford Kishore K. Bhakoo John B. Clark |
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Affiliation: | Department of Neurochemistry, Institute of Neurology, University College London, London, and; Medical Research Council, Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford, Oxford, England |
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Abstract: | Abstract: We have previously identified cerebellum to contain significantly higher levels, compared with other brain regions, of the mRNA encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). In this report, we extend these observations, using primary cultures of cerebellar astrocytes and cerebellar granule neurons, and show that mHS mRNA was not readily detected in these cell types, suggesting that other cerebellar cell types account for mHS mRNA abundances observed in cerebellum. In contrast, we report, for the first time, the ready detection of mHS mRNA together with the mRNAs encoding the remaining enzymes of the 3-hydroxy-3-methylglutaryl-CoA cycle, namely, mitochondrial acetoacetyl-CoA thiolase and 3-hydroxy-3-methylglutaryl-CoA lyase, in primary cultures of neonatal meningeal fibroblasts. Based on observations of the effects of fetal calf serum in the culture medium and the documented effects of various hormones on mHS mRNA levels in liver, we show that the glucocorticoid hydrocortisone effects a selective fourfold increase in mHS mRNA abundances in both neonatal meningeal fibroblasts and neonatal cortical astrocytes cultured in a serum-free/hormone-free medium. |
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Keywords: | Mitochondrial acetoacetyl-CoA thiolase Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 3-Hydroxy-3-methylglutaryl-CoA lyase RNase protection assay Astrocyte Meningeal fibroblast Ketogenic diet Seizure Epilepsy |
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