title: Glutamate levels control HT22 murine hippocampal cell death by regulating biphasic patterns of Erk1/2 activation: role of metabolic glutamate receptor 5.
abstract: Extracellular glutamate concentration is a critical determinant of neuronal cell fate. We recently demonstrated that HT22 murine hippocampal cell viability was reduced by exposure to high concentrations of glutamate, whereas low concentrations promoted cell survival. Extracellular signal-regulated kinase (Erk)1/2 activation by glutamate is important for both glutamate-induced cell death and survival. In this study, we investigated the role of glutamate-induced or hydrogen peroxide (H2O2)-induced Erk1/2 activation in HT22 cell fate determination. Glutamate and H2O2 treatment similarly induced early (<1 h) Erk1/2 phosphorylation regardless of concentration. On the other hand, persistent Erk1/2 phosphorylation (16-24 h) was observed only in the presence of excess glutamate. Only the latter contributed to glutamate-induced cell death, which involved metabolic glutamate receptor 5. Our findings suggest that glutamate concentration modulates two distinct phases of Erk1/2 activation, which can explain the glutamate concentration-dependent determination of HT22 cell fate.
authors.affiliation: a Department of Life Sciences , Graduate School of Life Sciences, Toyo University , Gunma , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sato
authors.affiliation: b Faculty of Life Sciences, Department of Applied Biosciences , Toyo University , Gunma , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamanaka
authors.affiliation: b Faculty of Life Sciences, Department of Applied Biosciences , Toyo University , Gunma , Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Asakura
authors.affiliation: a Department of Life Sciences , Graduate School of Life Sciences, Toyo University , Gunma , Japan.|b Faculty of Life Sciences, Department of Applied Biosciences , Toyo University , Gunma , Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nedachi
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D010766:Phosphorylation; D064529:Receptor, Metabotropic Glutamate 5
chemical_list: C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018698:Glutamic Acid
keywords: Erk1/2; HT22 cells; glutamate; mGluR1; mGluR5