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Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology
Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552727/ https://www.ncbi.nlm.nih.gov/pubmed/26317696 http://dx.doi.org/10.1371/journal.pone.0136847 |
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author | Thompson, John W. Wei, Jianqin Appau, Kweku Wang, Huilan Yu, Hong Spiga, Maria G. Graham, Regina M. Webster, Keith A. |
author_facet | Thompson, John W. Wei, Jianqin Appau, Kweku Wang, Huilan Yu, Hong Spiga, Maria G. Graham, Regina M. Webster, Keith A. |
author_sort | Thompson, John W. |
collection | PubMed |
description | Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and heart failure. Only mitochondrial-dependent programmed death actions have been described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase p300, increased acetylation of histones and the transcription factor GATA4, and conferred p300 and GATA4-sensitive cellular morphological changes. In intact Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4 acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart failure that was partially prevented by p300 inhibition with curcumin. The results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte morphology by activating nuclear p300 acetyltransferase activity and hyperacetylating histones and p300-selective transcription factors. |
format | Online Article Text |
id | pubmed-4552727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45527272015-09-10 Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology Thompson, John W. Wei, Jianqin Appau, Kweku Wang, Huilan Yu, Hong Spiga, Maria G. Graham, Regina M. Webster, Keith A. PLoS One Research Article Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and heart failure. Only mitochondrial-dependent programmed death actions have been described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase p300, increased acetylation of histones and the transcription factor GATA4, and conferred p300 and GATA4-sensitive cellular morphological changes. In intact Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4 acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart failure that was partially prevented by p300 inhibition with curcumin. The results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte morphology by activating nuclear p300 acetyltransferase activity and hyperacetylating histones and p300-selective transcription factors. Public Library of Science 2015-08-28 /pmc/articles/PMC4552727/ /pubmed/26317696 http://dx.doi.org/10.1371/journal.pone.0136847 Text en © 2015 Thompson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Thompson, John W. Wei, Jianqin Appau, Kweku Wang, Huilan Yu, Hong Spiga, Maria G. Graham, Regina M. Webster, Keith A. Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title | Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title_full | Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title_fullStr | Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title_full_unstemmed | Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title_short | Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology |
title_sort | bnip3 binds and activates p300: possible role in cardiac transcription and myocyte morphology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552727/ https://www.ncbi.nlm.nih.gov/pubmed/26317696 http://dx.doi.org/10.1371/journal.pone.0136847 |
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