| Abstract No.: | A-C1091 |
| Country: | Canada |
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| Title: | DOCOSAHEXAENOIC ACID REDUCES 6-OHDA- AND MPP+-INDUCED TRANSLOCATION OF NUR77 TO THE CYTOPLASM AND DECREASES CYTOTOXICITY |
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| Authors/Affiliations: | 1 Cindy Tremblay*; 2 Claude Rouillard; 1 Maria-Grazia Martinoli;
1 Department of Biochemistry and Research Group in Neuroscience, Trois-Rivières, QC, Canada, Université du Québec à Trois-Rivières, QC, Canada; 2 Neuroscience Research Unit, CHUQ Research Center, and Faculty of Medicine, Université Laval, Quebec, QC, Canada
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| Content: | Nurr1, Nur77 and Nor-1 compose the orphan subset of nuclear receptor and are closely associated to dopamine neurotransmission. Nur77 is a critical factor in dopamine-mediated neuroadaptation and is involved in programmed cell death as a pro- or anti-apoptotic factor. DHA is the most abundant n-3 polyunsaturated fatty acid in the brain and it is a ligand for the retinoid X receptor (RXR), which can heterodimerize with Nur77. Thus, DHA might modulate Nur77 cellular localisation and might prevent neurotoxin-induced cytotoxicity. The aim of our study was to evaluate the neuroprotective potential of docosahexaenoic acid (DHA) against 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) induced toxicity in PC12 cells. We also report the cellular localisation of Nur77 after the neurotoxins treatments. PC12 cells were exposed to 6-OHDA or MPP+ and the cytoprotective potential of DHA was quantified by measuring the lactate deshydrogenase (LDH) release in the supernatant. Expression of Nur77 was evaluated by Western Blot of nuclear and cytoplasmic protein fractions. Modifications in Nur77 distribution was expressed as cyto/nuclear ratio of Nur77 protein expression. We demonstrated that administration of MPP+ or 6-OHDA induces a time dependant translocation of Nur77 to the cytoplasm. Pre-treatment with DHA partly prevents this translocation and decreases the cytotoxicity induced by MPP+ or 6-OHDA in PC12 cells. These results clearly demonstrate that DHA is a potential neuroprotective molecule in a cellular model of Parkinson Disease and suggest intriguing cooperation between DHA and Nur77 towards cellular fate guidance. |
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