| Autor: |
Nango H; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Kosuge Y; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Yoshimura N; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Miyagishi H; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Kanazawa T; Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Hashizaki K; Laboratory of Physical Chemistry, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Suzuki T; Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan., Ishige K; Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. |
| Abstrakt: |
Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E 2 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 2 (PGD 2 ) on neuritogenesis in NSC-34 cells. Exposure to PGD 2 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 2 (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD 2 was converted to 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) under cell-free conditions. Exogenously applied 15d-PGJ 2 mimicked the effect of PGD 2 on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist, suppressed PGD 2 -induced neurite outgrowth. Moreover, PGD 2 and 15d-PGJ 2 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 2 induces neuritogenesis in NSC-34 cells and that PGD 2 -induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ 2 . |
