Tsuchiya Hiroyoshi, Hohjoh Hirofumi, Fujiwara Yoko, Sugimoto Yukihiko, Koshimizu Taka-Aki
Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Biochem Biophys Res Commun. 2016 Feb 19;470(4):804-10. doi: 10.1016/j.bbrc.2016.01.091. Epub 2016 Jan 26.
Prostaglandins (PGs) play important roles in diverse physiological processes in the central nervous system. PGD2 is the most abundant PG in the brain and acts through specific receptors, DP1 and CRTH2. We investigated the effects of PGD2 on the morphology of the hypothalamic cell line mHypoE-N37 (N37). In N37 cells, serum starvation induced neurite outgrowth and PGD2 elicited neurite retraction, although we failed to detect transcripts for DP1 and CRTH2. Such an effect of PGD2 was efficiently mimicked by its metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2. N-acetyl cysteine completely abolished the effect of PGD2, and reactive oxygen species (ROS) were considered to be important. Notably, neurite outgrowth was restored by PGD2 removal. These results suggest that PGD2 induces reversible neurite retraction in a ROS-mediated mechanism that does not involve any known receptor.
前列腺素（PGs）在中枢神经系统的多种生理过程中发挥重要作用。前列腺素D2（PGD2）是大脑中含量最丰富的PG，通过特异性受体DP1和CRTH2发挥作用。我们研究了PGD2对下丘脑细胞系mHypoE-N37（N37）形态的影响。在N37细胞中，血清饥饿诱导神经突生长，而PGD2引起神经突回缩，尽管我们未能检测到DP1和CRTH2的转录本。PGD2的这种作用被其代谢产物15-脱氧-Δ（12,14）-前列腺素J2有效模拟。N-乙酰半胱氨酸完全消除了PGD2的作用，活性氧（ROS）被认为很重要。值得注意的是，去除PGD2后神经突生长得以恢复。这些结果表明，PGD2通过一种不涉及任何已知受体的ROS介导机制诱导可逆的神经突回缩。
