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

Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E 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 D (PGD) on neuritogenesis in NSC-34 cells. Exposure to PGD 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 PGD (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD was converted to 15-deoxy-Δ-prostaglandin J (15d-PGJ) under cell-free conditions. Exogenously applied 15d-PGJ mimicked the effect of PGD on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist, suppressed PGD-induced neurite outgrowth. Moreover, PGD and 15d-PGJ 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 PGD induces neuritogenesis in NSC-34 cells and that PGD-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ.