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Title: Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors involves the AP-1 transcription factor
Authors: Santos, A. E. 
Duarte, C. B. 
Iizuka, M. 
Barsoumian, E. L. 
Ham, J. 
Lopes, M. C. 
Carvalho, A. P. 
Carvalho, A. L. 
Keywords: Excitotoxicity; Glutamate; Ca2+-permeable AMPA receptors; GluR4 subunit; Activator protein-1 (AP-1) transcription factor
Issue Date: Apr-2006
Publisher: Nature Publishing Group
Citation: Cell Death and Differentiation. 13:4 (2006) 652-660
Abstract: Cells preferentially expressing GluR4-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors are particularly sensitive to excitotoxicity mediated through non-N-methyl-D-aspartate receptors. However, the excitotoxic signalling pathways associated with GluR4-containing AMPA receptors are not known. In this work, we investigated the downstream signals coupled to excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors, using a HEK 293 cell line constitutively expressing the GluR4flip subunit of AMPA receptors (HEK-GluR4). Glutamate stimulation of GluR4-containing AMPA receptors decreased cell viability, in a calcium-dependent manner, when the receptor desensitisation was prevented with cyclothiazide. The excitotoxic stimulation mediated through GluR4-containing AMPA receptors increased activator protein-1 (AP-1) DNA-binding activity. Inhibition of the AP-1 activity by overexpression of a c-Jun dominant-negative form protected HEK-GluR4 cells against excitotoxic damage. Taken together, the results indicate that overactivation of Ca2+-permeable GluR4-containing AMPA receptors is coupled to a death pathway mediated, at least in part, by the AP-1 transcription factor
ISSN: 1350-9047
DOI: 10.1038/sj.cdd.4401785
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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