Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats.
Cell Death Dis
; 8(2): e2624, 2017 02 23.
Article
en En
| MEDLINE
| ID: mdl-28230854
ABSTRACT
Our recent study has revealed that the myocardin-related transcription factor-A (MRTF-A) is involved in the apoptosis of cortical neurons induced by ischemia/reperfusion (I/R). Histone deacetylase 5 (HDAC5) and histone acetyltransferase p300 (P300) are two well-known regulators for transcription factors; however, their roles in MRTF-A-related effect on neuronal injuries during I/R are still unclear. In this study, in a model rat cerebral I/R injury via middle cerebral artery occlusion and reperfusion, we found that the expression and activity of HDAC5 was upregulated, whereas p300 and MRTF-A were downregulated both in expression and activity during I/R. Their expression changes and the interaction of the MRTF-A with HDAC5 or p300 were further verified by double immunofluorescence and co-immunoprecipitation. In cultured neuronal apoptosis model induced by H2O2, MRTF-A exhibited an anti-apoptotic effect by enhancing the transcription of Bcl-2 and Mcl-1 via CArG box binding. MRTF-A-induced anti-apoptotic effect was effectively inhibited by HDAC5, but was significantly enhanced by p300. The results suggest that both HDAC5 and p300 are involved in MRTF-A-mediated effect on neuronal apoptosis during ischemia/reperfusion injury, but with opposite effects.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Daño por Reperfusión
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Apoptosis
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Proteína p300 Asociada a E1A
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Histona Desacetilasas
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Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2017
Tipo del documento:
Article