Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats.

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.

• Authors: Na Li, Qiong Yuan, Xiao-Lu Cao, Ying Zhang, Zhen-Li Min, Shi-Qiang Xu, Zhi-Jun Yu, Jing Cheng, Chunxiang Zhang, Xia-Min Hu
• Journal: Cell death & disease (Cell Death Dis) Vol. 8 Issue 2 Pg. e2624 (02 23 2017) ISSN: 2041-4889 [Electronic] England
• PMID: 28230854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myeloid Cell Leukemia Sequence 1 Protein
• Proto-Oncogene Proteins c-bcl-2
• Transcription Factors
• myocardin-related transcription factor-A, rat
• E1A-Associated p300 Protein
• Ep300 protein, rat
• Hdac5 protein, rat
• Histone Deacetylases

Topics

• Animals
• Apoptosis (physiology)
• E1A-Associated p300 Protein (metabolism)
• Histone Deacetylases (metabolism)
• Male
• Myeloid Cell Leukemia Sequence 1 Protein (metabolism)
• Neurons (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology)
• Transcription Factors (metabolism)
• Transcription, Genetic (physiology)