title: p38 Mitogen-Activated Protein Kinase Pathway Regulates Genes during Proliferation and Differentiation in Oligodendrocytes.
abstract: We have previously shown that p38 mitogen-activated protein kinase (p38 MAPK) is important for oligodendrocyte (OLG) differentiation and myelination. However, the precise cellular mechanisms by which p38 regulates OLG differentiation remain largely unknown. To determine whether p38 functions in part through transcriptional events in regulating OLG identity, we performed microarray analysis on differentiating oligodendrocyte progenitors (OLPs) treated with a p38 inhibitor. Consistent with a role in OLG differentiation, pharmacological inhibition of p38 down-regulated the transcription of genes that are involved in myelin biogenesis, transcriptional control and cell cycle. Proliferation assays showed that OLPs treated with the p38 inhibitor retained a proliferative capacity which could be induced upon application of mitogens demonstrating that after two days of p38-inhibition OLGs remained poised to continue mitosis. Together, our results suggest that the p38 pathway regulates gene transcription which can coordinate OLG differentiation. Our microarray dataset will provide a useful resource for future studies investigating the molecular mechanisms by which p38 regulates oligodendrocyte differentiation and myelination.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada, H3G 1Y6.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Haines
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, 3801 University St, Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Fulton
authors.affiliation: Terry Fox Molecular Oncology Group, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, and Departments of Oncology and Medicine, McGill University, Montreal, Quebec, Canada, H3T 1E2.
authors.forename: Stephane
authors.initials: S
authors.lastname: Richard
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada, H3G 1Y6.|Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, 3801 University St, Montreal, Quebec, Canada, H3A 2B4.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Almazan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048749:Cytokinesis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009186:Myelin Sheath / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole