| Abstract No.: | C-A3022 |
| Country: | Canada |
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| Title: | ROLE OF THE P38 MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) / MAPK-ACTIVATED PROTEIN KINASE 2 (MAPKAPK2) SIGNALING CASCADE IN OLIGODENDROCYTE DIFFERENTIATION |
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| Authors/Affiliations: | 1Jeffery D. Haines*; 1 Gabriela Fragoso;2 Walter E. Mushynski; 1 Guillermina Almazan;
1 McGill University, Dept of Biochemistry, Montreal, QC, Canada; 2 McGill University, Dept of Pharmacology & Therapeutics; Montreal, QC, Canada |
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| Content: | In addition to its role as a stress-activated kinase, p38 is involved in neural function and development. We previously demonstrated a fundamental role for p38 in peripheral myelination. Here, we explored the potential function of this kinase in oligodendrocyte differentiation. Rat oligodendrocytes were found to abundantly express p38α, and its reduction by small interfering RNA, or by treatment with the selective inhibitor PD169316 resulted in significant decreases in the expression of galactosylceramide (GalC), sulfatide (sGalC), and myelin-specific proteins: myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and proteolipid protein (PLP). We found that p38 activity must be inhibited early in the differentiation of OLG to exhibit maximal effect on the block of myelin marker accumulation. Quantitative analysis of mRNA transcripts using real-time PCR revealed significant decreases in MBP, MAG, and PLP. We also observed a significant reduction in transcript levels for the glycosyltransferase responsible for GalC production, explaining the observed decreases in GalC and sGalC levels. We extend these findings by demonstrating that MAPKAPK2 is involved in the signaling pathway controlling oligodendrocyte differentiation. Further studies are underway to understand how p38 and MAPKAPK2 regulate oligodendrocyte differentiation and myelination.
This project is funded by the Multiple Sclerosis Society of Canada.
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