title: Involvement of extracellular signal-regulated protein kinase in gliosis induced during recovery from metabolic inhibition.
abstract: Brain reperfusion may be of particular importance in the etiology of periventricular leukomalacia, of which the common findings are gliosis and ventricular dilatation. To investigate the mechanism of this pathogenesis, we used a metabolic inhibition (MI) model using cyanide plus deoxyglucose treatment of cultured glia isolated from fetal rat brain and examined the activity of extracellular signal-regulated protein kinase (ERK) during MI and also during the recovery from MI of 30 min. ERK activation was stimulated during MI and the recovery from MI. The time course and extent of activation of ERK during MI and the recovery from MI, however, were distinctly different. Activation of ERK was stimulated within 5 min of MI and declined thereafter. Activation of ERK was sustained during the recovery phase from MI and the extent of the activation was much greater than that during MI. Pretreatment with EGTA to eliminate extracellular Ca(2+), or with APV, an NMDA receptor antagonist, to inhibit Ca(2+) influx through the NMDA receptor, attenuated the activation of ERK. Moreover, pretreatment with PMA to downregulate PKC abolished the activation of ERK. PD98059, an inhibitor of ERK kinase, attenuated the cell proliferation induced by MI followed by recovery from MI. These results suggest that ERK is involved in gliosis during the recovery phase from MI and may play a role in the etiology of periventricular leukomalacia.
authors.affiliation: Department of Obstetrics, Osaka University Medical School, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan. masa@gyne.med.osaka-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Masuhara
authors.forename: M
authors.initials: M
authors.lastname: Ohmichi
authors.forename: H
authors.initials: H
authors.lastname: Kurachi
authors.forename: K
authors.initials: K
authors.lastname: Tasaka
authors.forename: T
authors.initials: T
authors.lastname: Kanzaki
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: J
authors.initials: J
authors.lastname: Hayakawa
authors.forename: K
authors.initials: K
authors.lastname: Hisamoto
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: Y
authors.initials: Y
authors.lastname: Murata
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003847:Deoxyglucose / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004622:Embryo, Mammalian; D005911:Gliosis; D006624:Hippocampus / Q000166:cytology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019579:Neocortex / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012966:Sodium Cyanide / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D004533:Egtazic Acid; D015763:2-Amino-5-phosphonovalerate; D003847:Deoxyglucose; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D012966:Sodium Cyanide; D002118:Calcium