title: 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.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Min
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Shi-Qiang
authors.initials: SQ
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.|Drug Research Base of Cardiovascular and Cerebral Vascular, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China.
authors.forename: Xia-Min
authors.initials: XM
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C557977:myocardin-related transcription factor-A, rat; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat; C498619:Hdac5 protein, rat; D006655:Histone Deacetylases