The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells.

ABSTRACT

Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E2 promotes neurite outgrowth in NSC-34 cells, which are a model for motor neuron development. However, the effects of other prostaglandins on neuronal differentiation are poorly understood. The present study investigated the effect of prostaglandin D2 (PGD2) on neuritogenesis in NSC-34 cells. Exposure to PGD2 resulted in increased percentages of neurite-bearing cells and neurite length. Although D-prostanoid receptor (DP) 1 and DP2 were dominantly expressed in the cells, BW245C (a DP1 agonist) and 15(R)-15-methyl PGD2 (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD2 was converted to 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) under cell-free conditions. Exogenously applied 15d-PGJ2 mimicked the effect of PGD2 on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist, suppressed PGD2-induced neurite outgrowth. Moreover, PGD2 and 15d-PGJ2 increased the protein expression of Islet-1 (the earliest marker of developing motor neurons), and these increases were suppressed by co-treatment with GW9662. These results suggest that PGD2 induces neuritogenesis in NSC-34 cells and that PGD2-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ2.