title: Prostaglandin D2 elicits the reversible neurite retraction in hypothalamic cell line.
abstract: 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.
authors.affiliation: Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan. Electronic address: tutty@jichi.ac.jp.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hohjoh
authors.affiliation: Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Division of Molecular Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Koshimizu
mesh_terms: D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015230:Prostaglandin D2 / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D015230:Prostaglandin D2
keywords: 15d-PGJ(2); Neurite retraction; PGD(2); ROS