Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 2019-2024, 2012.
Article
em En
| WPRIM
| ID: wpr-283676
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Activation of c-Jun NH(2)-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI). However, the underlying molecular pathway remains unclear. Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.</p><p><b>METHODS</b>A total of 186 male Sprague-Dawley (SD) rats (300 - 350 g) were used in this study. By randomized block method rats were randomly divided into four groups sham-operated (n = 46), TBI (n = 60), TBI + dimethyl sulfoxide (DMSO) (n = 40), and TBI + SP600125 (n = 40). JNK was treated with SP600125, a specific JNK inhibitor. JNK, p-P53, Beclin-1, damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis. The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry, and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation. Multiple-group comparisons were conducted using analysis of variance (ANOVA). P values of less than 0.05 were considered statistically significant.</p><p><b>RESULTS</b>It was observed that the expression of JNK, p-P53, Beclin-1, DRAM and p-bcl-2 was increasing after TBI, and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons. But these were significantly inhibited in SP600125 group compared with sham group and TBI + SP600125 group (P < 0.05). The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI.</p><p><b>CONCLUSION</b>JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.</p>
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Fosforilação
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Autofagia
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Lesões Encefálicas
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Western Blotting
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Proteína Supressora de Tumor p53
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Imunofluorescência
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Ratos Sprague-Dawley
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Proteínas Proto-Oncogênicas c-bcl-2
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Biologia Celular
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Proteínas Quinases JNK Ativadas por Mitógeno
Limite:
Animals
Idioma:
En
Revista:
Chinese Medical Journal
Ano de publicação:
2012
Tipo de documento:
Article
País de publicação:
CHINA
/
CN
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REPUBLIC OF CHINA