A PPARs cross-talk concertedly commits C6 glioma cells to oligodendrocytes and induces enzymes involved in myelin synthesis
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Date
2008
Journal Title
Journal ISSN
Volume Title
Publisher
WILEY
Abstract
Peroxisome proliferator activated receptors (PPARs, alpha, beta/delta, gamma) control lipid homeostasis and differentiation in various tissues and tumor cells. PPAR beta and PPAR gamma increase oligodendrocyte maturation in glial mixed populations and spinal cord oligodendrocytes, respectively, and PPAR beta is known to modulate the activity of other PPARs. To assess a possible interaction between PPARs in glial cell differentiation we used the undifferentiated C6 glioma cell line as model. These cells express all three PPARs, but only PPAR gamma shows transcriptional activity in agonist-based reporter gene assay. Agonist-activated PPAR gamma up-regulates oligodendrocyte markers, down-regulates an astrocyte marker, and increases alkyl-dihydroxyacetone phosphate synthase, enzyme involved in the synthesis of myelin-rich plasmalogens. Similar effects are induced in PPAR gamma overexpressing cells, which in addition show PPAR beta up-regulation. PPAR beta or PPAR alpha agonists show no effect. Nevertheless, PPAR beta overexpression up-regulates PPAR gamma and commits C6 cells to oligodendrocytes: effect that is abrogated by a PPAR gamma antagonist or PPAR gamma interference RNA. Moreover, PPAR beta overexpression also induces PPAR alpha and its target genes, including acyl-CoA oxidase, enzyme involved in very long chain fatty acid recycling, and in the synthesis of myelin components such as docosahexaenoic acid. These results indicate for the first time, that PPARs concertedly cooperate in C6 glioma cell differentiation to oligodendrocytes. Further, they suggest that active PPAR beta might be essential for increasing oligodendrocyte distinctive markers and enzymes required for myelin synthesis in C6 glioma cells through up-regulation of PPAR gamma and PPAR alpha.
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Keywords
ACTIVATED-RECEPTOR-GAMMA, MESSENGER-RNAS, TARGETED DISRUPTION, PEROXISOME, GROWTH, RAT, EXPRESSION, ALPHA, DELTA, BETA