TY - JOUR
T1 - Role of RXR in neurite outgrowth induced by docosahexaenoic acid
AU - Calderon, Frances
AU - Kim, Hee Yong
N1 - Funding Information:
We thank Dr. Henry L. Puhl III from the Section on Transmitter Signaling, Laboratory of Molecular Physiology, NIAAA for his expert assistance on the DLR assay. This work was supported by the intramural program of the National Institute on Alcohol Abuse and Alcoholism, NIH.
PY - 2007/11
Y1 - 2007/11
N2 - 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-α, -β1, -β2, and -γ, are expressed exclusively in neurons with distinctive intracellular distribution. The cell-based dual luciferase reporter assay indicated that DHA activates RXR-α at or above 10 μM but not at 1.5 μM where DHA induces neurite outgrowth. Arachidonic acid also activated RXR-α 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-α, although involvement of other isoforms or DHA metabolites cannot be excluded.
AB - 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-α, -β1, -β2, and -γ, are expressed exclusively in neurons with distinctive intracellular distribution. The cell-based dual luciferase reporter assay indicated that DHA activates RXR-α at or above 10 μM but not at 1.5 μM where DHA induces neurite outgrowth. Arachidonic acid also activated RXR-α 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-α, although involvement of other isoforms or DHA metabolites cannot be excluded.
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U2 - 10.1016/j.plefa.2007.10.026
DO - 10.1016/j.plefa.2007.10.026
M3 - Article
C2 - 18036800
AN - SCOPUS:36649005003
SN - 0952-3278
VL - 77
SP - 227
EP - 232
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 5-6
ER -