title: N-methyl-D-aspartate induces phosphorylation of cAMP response element (CRE)-binding protein and increases DNA-binding activity of CRE in rat retina.
abstract: The aim of this study was to investigate whether an excitotoxic concentration of N-methyl-D-aspartate (NMDA) increases the expression of the phosphorylated cAMP response element-binding protein (p-CREB) and the DNA-binding activity of the cAMP response element (CRE) in rat retina. Intravitreal injection of NMDA was performed in adult male Wistar rats. p-CREB protein levels in the retina were examined by Western blot analysis. DNA-binding activity of CRE in the retina was evaluated by an electrophoretic mobility gel shift assay (EMSA). We confirmed that NMDA induced the reduction of ganglion cells and the inner plexiform layer of the retina. Western blot analysis showed increases in the expression of p-CREB in the retina 12 and 24 h after intravitreal NMDA injection and dimer formation of CREB in the nuclear fraction at 24 h. Increases of DNA-binding activity were observed in the retina 24 h after NMDA injection by EMSA. Our results suggest that phosphorylation of CREB may involved in NMDA-induced excitotoxicity in rat retina. Phosphorylated CREB seems to be the active form and the one that is transcribed.
authors.affiliation: Department of Ophthalmology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. isenoumi@marianna-u.ac.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Isenoumi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaoka
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Motoki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kitaoka
authors.forename: Kohei
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Munemasa
authors.forename: Jiro
authors.initials: J
authors.lastname: Kogo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Satoki
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016202:N-Methylaspartate; D004247:DNA