Early c-Jun N-terminal kinase-dependent phosphorylation of activating transcription factor-2 is associated with degeneration of retinal ganglion cells.
Neuroscience
; 180: 64-74, 2011 Apr 28.
Article
em En
| MEDLINE
| ID: mdl-21300140
Neuron death due to deprivation of target-derived neurotrophic factors depends on protein synthesis regulated by transcription factor activity. We investigated the content and phosphorylation of activating transcription factor 2 (ATF-2) in axon-damaged retinal ganglion cells of neonatal rats. In the retina of neonatal rats, the ATF-2 protein is predominantly located in the nucleus of the ganglion cells. A gradual loss of the immunoreactivity for ATF-2 occurred after explantation. ATF-2 is phosphorylated early after explantation, with a peak within 3 hours, preceding the peak of cell death that occurs at 18 hours. Both the phosphorylation of ATF-2 and ganglion cell death were blocked by treatment with an inhibitor of c-Jun N-terminal kinase (JNK), whereas an inhibitor of p38 reduced only slightly the rate of ganglion cell death with no effect upon phosphorylation of ATF-2. Inhibitors of phosphatidyl inositol 3 kinase (PI-3K), protein kinase C (PKC) or extracellular regulated kinase (ERK) had no effect. Finally, the inhibitor of JNK blocked the upregulation of both c-Jun and Hrk in the GCL after retinal explantation. The data show that phosphorylation of ATF-2 by JNK is associated with retinal ganglion cell death after axon damage.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Ganglionares da Retina
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Proteínas Quinases JNK Ativadas por Mitógeno
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Fator 2 Ativador da Transcrição
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Degeneração Neural
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Neuroscience
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos