Role of RXR in neurite outgrowth induced by docosahexaenoic acid.
We have previously demonstrated that docosahexaenoic acid (DHA) at low micromolar concentrations has a remarkable effect on morphological differentiation of hippocampal neurons by increasing the population of neurons with more branches and longer neurites. In this study, possible involvement of the retinoid X receptor (RXR) in the DHA-induced hippocampal neurite outgrowth was evaluated as DHA is an endogenous ligand for RXR. Immunocytochemical examination revealed that all RXR isoforms, RXR-alpha, -beta(1), -beta(2), and -gamma, are expressed exclusively in neurons with distinctive intracellular distribution. The cell-based dual luciferase reporter assay indicated that DHA activates RXR-alpha at or above 10 microM but not at 1.5 microM where DHA induces neurite outgrowth. Arachidonic acid also activated RXR-alpha in a similar concentration range but with lower efficacy. Our results suggest that DHA-induced neurite outgrowth may not be mediated by direct activation of RXR-alpha, although involvement of other isoforms or DHA metabolites cannot be excluded.
Laboratory of Molecular Signaling, NIAAA, NIH, 5625 Fishers Lane, 3N-07, Bethesda, MD 20892-9410, USA.
Frances
F
Calderon
Hee-Yong
HY
Kim
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism*
D020033:Protein Isoforms; D047490:Retinoid X Receptor alpha; D047488:Retinoid X Receptors; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid