AP-1 activity during the growth, differentiation, and death of O-2A lineage cells.
Oligodendrocyte differentiation has been correlated with AP-1 activity, being low in progenitors and high in differentiated cells. In this study we have carried out a detailed temporal analysis of AP-1 activity in oligodendrocyte-type-2 astrocyte (O-2A) lineage cells. We show that low AP-1 activity in progenitor cells depended on the application of growth factors. Treatment of cells with B104-conditioned medium induced high AP-1 activity, increased process length, and improved growth. The role of AP-1 in proliferation and process extension was emphasized when progenitor cells overexpressing a c-Jun dominant-negative mutant had impaired growth and shortened processes. AP-1 DNA-binding activity during O-2A differentiation in vitro showed an initial down-regulation followed by up-regulation after 2 days. Increased AP-1 levels in oligodendrocytes were inhibited by overexpression of bcl-2, indicating that AP-1 in mature oligodendrocytes is involved in the regulation of apoptosis. Prevention of cell death by bcl-2 in oligodendrocytes was accompanied by progressive differentiation and expression of MOG and PLP.
FitzGerald
U F
UF
Department of Neurology, University of Glasgow, United Kingdom.
Barnett
S C
SC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005799:Genes, Dominant; D016758:Genes, jun / Q000502:physiology; D016259:Genes, myc / Q000502:physiology; D066298:In Vitro Techniques; D009447:Neuroblastoma; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016596:Vinculin / Q000235:genetics
D017077:Culture Media, Conditioned; D019253:Proto-Oncogene Proteins c-bcl-2; D018808:Transcription Factor AP-1; D016596:Vinculin