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https://hdl.handle.net/10316/12659
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 | URI: | https://hdl.handle.net/10316/12659 | 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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