title: Identification of a prostaglandin D2 metabolite as a neuritogenesis enhancer targeting the TRPV1 ion channel.
abstract: Mast cells play important roles in allergic inflammation by secreting various mediators. In the present study, based on the finding that the medium conditioned by activated RBL-2H3 mast cells enhanced the nerve growth factor (NGF)-induced neuritogenesis of PC12 cells, we attempted to isolate an active compound from the mast cell conditioned culture medium. Our experiment identified 15-deoxy-Δ(12,14)-PGJ2 (15d-PGJ2), one of the PGD2 metabolites, as a potential enhancer of neuritogenesis. 15d-PGJ2 strongly enhanced the neuritogenesis elicited by a low-concentration of NGF that alone was insufficient to induce the neuronal differentiation. This 15d-PGJ2 effect was exerted in a Ca(2+)-dependent manner, but independently of the NGF receptor TrkA. Importantly, 15d-PGJ2 activated the transient receptor potential vanilloid-type 1 (TRPV1), a non-selective cation channel, leading to the Ca(2+) influx. In addition, we observed that (i) NGF promoted the insertion of TRPV1 into the cell surface membrane and (ii) 15d-PGJ2 covalently bound to TRPV1. These findings suggest that the NGF/15d-PGJ2-induced neuritogenesis may be regulated by two sets of mechanisms, one for the translocation of TRPV1 into the cell surface by NGF and one for the activation of TRPV1 by 15d-PGJ2. Thus, there is most likely a link between allergic inflammation and activation of the neuronal differentiation.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.|PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Inuzuka
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Nakashima
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kozai
authors.affiliation: Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D017077:Culture Media, Conditioned; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008407:Mast Cells / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: C477819:15-deoxyprostaglandin J2; D017077:Culture Media, Conditioned; D008024:Ligands; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D020932:Nerve Growth Factor; D015230:Prostaglandin D2; D002118:Calcium