PPAR gamma activators induce growth arrest and process extension in B12 oligodendrocyte-like cells and terminal differentiation of cultured oligodendrocytes.
Peroxisome proliferator-activated receptors (PPARs) are key transcription factors in the control of lipid homeostasis and cell differentiation, but little is known about their function in oligodendrocytes, the major lipid-synthesizing cells in the central nervous system (CNS). Using the B12 oligodendrocyte-like cell line and rat spinal cord-derived oligodendrocytes, we evaluated the importance of PPARgamma in the maturation process of these cells. B12 cells express all PPAR isoforms (alpha, beta/delta, and gamma), as assessed by RT-PCR, Western-blot, and transactivation assays. B12 cells respond specifically to PPARgamma agonists by arresting cell proliferation and extending cell processes, events that are blocked by the PPARgamma antagonist GW9662. In addition, alkyl-dihydroxyacetone phosphate synthase (ADAPS), a key peroxisomal enzyme involved in the synthesis of myelin-rich lipid plasmalogens, is increased in PPARgamma agonist-treated B12 cells. In contrast with B12 cells, both immature and mature isolated spinal cord oligodendrocytes presented a high and similar expression level of ADAPS, as assessed by immunocytochemistry. However, as in B12 cells, isolated spinal cord oligodendrocytes were also found to respond specifically to PPARgamma agonists with a four-fold increase in the number of mature cells. Our data suggest a relevant role for PPARgamma in oligodendrocyte lipid metabolism and differentiation.
Roth
Alejandro D
AD
Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
Leisewitz
Andrea V
AV
Jung
Juan E
JE
Cassina
Patricia
P
Barbeito
Luis
L
Inestrosa
Nibaldo C
NC
Bronfman
Miguel
M
D019883:Alkyl and Aryl Transferases / Q000187:drug effects / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D020033:Protein Isoforms; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019883:Alkyl and Aryl Transferases; C019654:alkylglycerone-phosphate synthase