A PPARs cross-talk concertedly commits C6 glioma cells to oligodendrocytes and induces enzymes involved in myelin synthesis.
Peroxisome proliferator activated receptors (PPARs, alpha, beta/delta, gamma) control lipid homeostasis and differentiation in various tissues and tumor cells. PPARbeta and PPARgamma increase oligodendrocyte maturation in glial mixed populations and spinal cord oligodendrocytes, respectively, and PPARbeta 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 PPARgamma shows transcriptional activity in agonist-based reporter gene assay. Agonist-activated PPARgamma 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 PPARgamma overexpressing cells, which in addition show PPARbeta up-regulation. PPARbeta or PPARalpha agonists show no effect. Nevertheless, PPARbeta overexpression up-regulates PPARgamma and commits C6 cells to oligodendrocytes; effect that is abrogated by a PPARgamma antagonist or PPARgamma interference RNA. Moreover, PPARbeta overexpression also induces PPARalpha 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 PPARbeta might be essential for increasing oligodendrocyte distinctive markers and enzymes required for myelin synthesis in C6 glioma cells through up-regulation of PPARgamma and PPARalpha.
Facultad de Ciencias Biologicas, Department of Cellular and Molecular Biology, Centro de Regulación Celular y Patologia (CRCP), Millennium Institute for Fundamental and Applied Biology, P.Universidad Catolica de Chile, Alameda, Santiago, Chile.
Andrea V
AV
Leisewitz
Carolina R
CR
Urrutia
Gabriela R
GR
Martinez
Gloria
G
Loyola
Miguel
M
Bronfman
D019883:Alkyl and Aryl Transferases / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019070:Cell Lineage; D004790:Enzyme Induction; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020239:Receptor Cross-Talk; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
C503394:GW 610742; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006253:pirinixic acid; D019883:Alkyl and Aryl Transferases; C019654:alkylglycerone-phosphate synthase