Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy

Pathological cardiac hypertrophy is a classical hallmark of heart failure. At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it...

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Veröffentlicht in:The Journal of nutritional biochemistry 2020-05, Vol.79, p.108339-108339, Article 108339
Hauptverfasser: Evans, Levi W., Bender, Abigail, Burnett, Leah, Godoy, Luis, Shen, Yi, Staten, Dante, Zhou, Tong, Angermann, Jeffrey E., Ferguson, Bradley S.
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container_issue
container_start_page 108339
container_title The Journal of nutritional biochemistry
container_volume 79
creator Evans, Levi W.
Bender, Abigail
Burnett, Leah
Godoy, Luis
Shen, Yi
Staten, Dante
Zhou, Tong
Angermann, Jeffrey E.
Ferguson, Bradley S.
description Pathological cardiac hypertrophy is a classical hallmark of heart failure. At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it is not known if the cardio-protective actions for emodin are mediated through HDAC-dependent regulation of gene expression. Therefore, we hypothesized that emodin would attenuate pathological cardiac hypertrophy via inhibition of HDACs, and that these actions would be reflected in an emodin-rich food like rhubarb. In this study, we demonstrate that emodin and Turkish rhubarb containing emodin inhibit HDAC activity in vitro, with fast-on, slow-off kinetics. Moreover, we show that emodin increased histone acetylation in cardiomyocytes concomitant to global changes in gene expression; gene expression changes were similar to the well-established pan-HDAC inhibitor trichostatin A (TSA). We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. These data suggest that emodin blocked pathological cardiac hypertrophy, in part, by inhibiting HDAC-dependent gene expression changes.
doi_str_mv 10.1016/j.jnutbio.2019.108339
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At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it is not known if the cardio-protective actions for emodin are mediated through HDAC-dependent regulation of gene expression. Therefore, we hypothesized that emodin would attenuate pathological cardiac hypertrophy via inhibition of HDACs, and that these actions would be reflected in an emodin-rich food like rhubarb. In this study, we demonstrate that emodin and Turkish rhubarb containing emodin inhibit HDAC activity in vitro, with fast-on, slow-off kinetics. Moreover, we show that emodin increased histone acetylation in cardiomyocytes concomitant to global changes in gene expression; gene expression changes were similar to the well-established pan-HDAC inhibitor trichostatin A (TSA). We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. 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At the molecular level, inhibition of histone deacetylase (HDAC) enzymes attenuate pathological cardiac hypertrophy in vitro and in vivo. Emodin is an anthraquinone that has been implicated in cardiac protection. However, it is not known if the cardio-protective actions for emodin are mediated through HDAC-dependent regulation of gene expression. Therefore, we hypothesized that emodin would attenuate pathological cardiac hypertrophy via inhibition of HDACs, and that these actions would be reflected in an emodin-rich food like rhubarb. In this study, we demonstrate that emodin and Turkish rhubarb containing emodin inhibit HDAC activity in vitro, with fast-on, slow-off kinetics. Moreover, we show that emodin increased histone acetylation in cardiomyocytes concomitant to global changes in gene expression; gene expression changes were similar to the well-established pan-HDAC inhibitor trichostatin A (TSA). We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. 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We additionally present evidence that emodin inhibited phenylephrine (PE) and phorbol myristate acetate (PMA)-induced hypertrophy in neonatal rat ventricular myocytes (NRVMs). Lastly, we demonstrate that the cardioprotective actions of emodin are translated to an angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition. These data suggest that emodin blocked pathological cardiac hypertrophy, in part, by inhibiting HDAC-dependent gene expression changes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32007664</pmid><doi>10.1016/j.jnutbio.2019.108339</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects acetates
Acetylation
angiotensin II
Angiotensin II - pharmacology
animal disease models
Animals
Animals, Newborn
Cardiac hypertrophy
Cardiomegaly - drug therapy
Cardiomegaly - metabolism
cardiomyocytes
Cardiotonic Agents - pharmacology
Disease Models, Animal
Emodin
Emodin - pharmacology
enzyme inhibition
Female
fibrosis
Food bioactives
gene expression
Gene Expression - drug effects
gene expression regulation
HDAC
Heart failure
Histone deacetylase
Histone Deacetylase Inhibitors - pharmacology
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
histones
Humans
Hydroxamic Acids - pharmacology
hypertrophy
Male
Mice
Mice, Inbred C57BL
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
phenylephrine
Rats
Rats, Sprague-Dawley
Rheum - chemistry
rhubarb
title Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy
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