title: Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources.
abstract: Abstract Cerebrospinal fluid (CSF) induced neurite retraction of differentiated PC12 cells; the action was observed in 15 min (a rapid response) and the activity further increased until 6 h (a long-acting response) during exposure of CSF to the cells. The CSF action was sensitive to monoglyceride lipase and diminished by homologous desensitization with lysophosphatidic acid (LPA) and by pretreatment with an LPA receptor antagonist Ki16425. Although fresh CSF contains LPA to some extent, the LPA content in the medium was increased during culture of PC12 cells with CSF. The rapid response was mimicked by exogenous LPA, and a long-acting response was duplicated by a recombinant autotaxin, lysophospholipase D (lyso-PLD). Although the lyso-PLD substrate lysophosphatidylcholine (LPC) was not detected in CSF, lyso-PLD activity and an approximately 120-kDa autotaxin protein were detected in CSF. On the other hand, LPC but not lyso-PLD activity was detected in the conditioned medium of a PC12 cell culture without CSF. Among neural cells examined, leptomeningeal cells expressed the highest lyso-PLD activity and autotaxin protein. These results suggest that leptomeningeal cells may work as one of the sources for autotaxin, which may play a critical role in LPA production and thereby regulate axonal and neurite morphological change.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. kosato@showa.gunma-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Enkhzol
authors.initials: E
authors.lastname: Malchinkhuu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muraki
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Hayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tosaka
authors.forename: Akikazu
authors.initials: A
authors.lastname: Mochiduki
authors.forename: Kinji
authors.initials: K
authors.lastname: Inoue
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nochi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamoto
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D005956:Glucose-6-Phosphate Isomerase / Q000134:cerebrospinal fluid* / Q000502:physiology*; D006023:Glycoproteins / Q000134:cerebrospinal fluid* / Q000502:physiology*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000134:cerebrospinal fluid* / Q000502:physiology*; D016501:Neurites / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011422:Propionates / Q000494:pharmacology; D011755:Pyrophosphatases; D051381:Rats; D017208:Rats, Wistar; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D007555:Isoxazoles; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011422:Propionates; D011755:Pyrophosphatases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; C032881:lysophosphatidic acid