N-Methyl-D-aspartate Induces Phosphorylation of cAMP Response Element (CRE)-Binding Protein and Increases DNA-Binding Activity of CRE in Rat Retina

Autor: Kazuyuki Isenoumi, Toshio Kumai, Yasushi Kitaoka, Masamitsu Motoki, Yuka Kitaoka, Kohei Kuribayashi, Yasunari Munemasa, Jiro Kogo, Shinichi Kobayashi, Satoki Ueno
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Journal of Pharmacological Sciences, Vol 95, Iss 1, Pp 108-114 (2004)
Druh dokumentu: article
ISSN: 1347-8613
DOI: 10.1254/jphs.95.108
Popis: 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. Keywords:: cAMP response element-binding protein, glaucoma, N-methyl-D-aspartate, phosphorylation, retina
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