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

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 fac...

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Autores principales: Li, Na, Yuan, Qiong, Cao, Xiao-Lu, Zhang, Ying, Min, Zhen-Li, Xu, Shi-Qiang, Yu, Zhi-Jun, Cheng, Jing, Zhang, Chunxiang, Hu, Xia-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386465/
https://www.ncbi.nlm.nih.gov/pubmed/28230854
http://dx.doi.org/10.1038/cddis.2017.16
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author Li, Na
Yuan, Qiong
Cao, Xiao-Lu
Zhang, Ying
Min, Zhen-Li
Xu, Shi-Qiang
Yu, Zhi-Jun
Cheng, Jing
Zhang, Chunxiang
Hu, Xia-Min
author_facet Li, Na
Yuan, Qiong
Cao, Xiao-Lu
Zhang, Ying
Min, Zhen-Li
Xu, Shi-Qiang
Yu, Zhi-Jun
Cheng, Jing
Zhang, Chunxiang
Hu, Xia-Min
author_sort Li, Na
collection PubMed
description 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 H(2)O(2), 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.
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spelling pubmed-53864652017-04-26 Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats Li, Na Yuan, Qiong Cao, Xiao-Lu Zhang, Ying Min, Zhen-Li Xu, Shi-Qiang Yu, Zhi-Jun Cheng, Jing Zhang, Chunxiang Hu, Xia-Min Cell Death Dis Original Article 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 H(2)O(2), 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. Nature Publishing Group 2017-02 2017-02-23 /pmc/articles/PMC5386465/ /pubmed/28230854 http://dx.doi.org/10.1038/cddis.2017.16 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Li, Na
Yuan, Qiong
Cao, Xiao-Lu
Zhang, Ying
Min, Zhen-Li
Xu, Shi-Qiang
Yu, Zhi-Jun
Cheng, Jing
Zhang, Chunxiang
Hu, Xia-Min
Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title_full Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title_fullStr Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title_full_unstemmed Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title_short Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats
title_sort opposite effects of hdac5 and p300 on mrtf-a-related neuronal apoptosis during ischemia/reperfusion injury in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386465/
https://www.ncbi.nlm.nih.gov/pubmed/28230854
http://dx.doi.org/10.1038/cddis.2017.16
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