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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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. |
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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. These data suggest that emodin blocked pathological cardiac hypertrophy, in part, by inhibiting HDAC-dependent gene expression changes.</description><identifier>ISSN: 0955-2863</identifier><identifier>EISSN: 1873-4847</identifier><identifier>DOI: 10.1016/j.jnutbio.2019.108339</identifier><identifier>PMID: 32007664</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>The Journal of nutritional biochemistry, 2020-05, Vol.79, p.108339-108339, Article 108339</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-8098c5b170462436f9aa5d557e32ec3dc2c02838bec68f61dd28088fd1b41d093</citedby><cites>FETCH-LOGICAL-c500t-8098c5b170462436f9aa5d557e32ec3dc2c02838bec68f61dd28088fd1b41d093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0955286319308897$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32007664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Evans, Levi W.</creatorcontrib><creatorcontrib>Bender, Abigail</creatorcontrib><creatorcontrib>Burnett, Leah</creatorcontrib><creatorcontrib>Godoy, Luis</creatorcontrib><creatorcontrib>Shen, Yi</creatorcontrib><creatorcontrib>Staten, Dante</creatorcontrib><creatorcontrib>Zhou, Tong</creatorcontrib><creatorcontrib>Angermann, Jeffrey E.</creatorcontrib><creatorcontrib>Ferguson, Bradley S.</creatorcontrib><title>Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy</title><title>The Journal of nutritional biochemistry</title><addtitle>J Nutr Biochem</addtitle><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.</description><subject>acetates</subject><subject>Acetylation</subject><subject>angiotensin II</subject><subject>Angiotensin II - pharmacology</subject><subject>animal disease models</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Cardiac hypertrophy</subject><subject>Cardiomegaly - drug therapy</subject><subject>Cardiomegaly - metabolism</subject><subject>cardiomyocytes</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Emodin</subject><subject>Emodin - pharmacology</subject><subject>enzyme inhibition</subject><subject>Female</subject><subject>fibrosis</subject><subject>Food bioactives</subject><subject>gene expression</subject><subject>Gene Expression - drug effects</subject><subject>gene expression regulation</subject><subject>HDAC</subject><subject>Heart failure</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylase Inhibitors - pharmacology</subject><subject>Histone Deacetylases - genetics</subject><subject>Histone Deacetylases - metabolism</subject><subject>histones</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>hypertrophy</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>phenylephrine</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rheum - chemistry</subject><subject>rhubarb</subject><issn>0955-2863</issn><issn>1873-4847</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhJ4B8LIcs_ogd5wKqlpZWqtRLOVuOPSFeknixnZXy78l2txWceprRzDvvjOZB6CMla0qo_LJdb8cpNz6sGaH1UlOc16_QiqqKF6Uqq9doRWohCqYkP0PvUtoSQlgp5Ft0xhkhlZTlCv2-GoLzIzajw_CYFtHbDsduakxssB873_iccOdTDiNgB8ZCnnuTAF_cfL_cfMbGZr_3eX40sSY6bywe5mDnDLibdxBzDLtufo_etKZP8OEUz9HP66uHzU1xd__jdnN5V1hBSC4UqZUVDa1IKVnJZVsbI5wQFXAGljvLLGGKqwasVK2kzjFFlGodbUrqSM3P0dej725qBnAWxhxNr3fRDybOOhiv_--MvtO_wl5XVLKKHQwuTgYx_JkgZT34ZKHvzQhhSnq5quZVXSq2SMVRamNIKUL7vIYSfQClt_oESh9A6SOoZe7Tvzc-Tz2RWQTfjgJYPrX3EHWyHkYLzkewWbvgX1jxFx4XqVo</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Evans, Levi W.</creator><creator>Bender, Abigail</creator><creator>Burnett, Leah</creator><creator>Godoy, Luis</creator><creator>Shen, Yi</creator><creator>Staten, Dante</creator><creator>Zhou, Tong</creator><creator>Angermann, Jeffrey E.</creator><creator>Ferguson, Bradley S.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20200501</creationdate><title>Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy</title><author>Evans, Levi W. ; Bender, Abigail ; Burnett, Leah ; Godoy, Luis ; Shen, Yi ; Staten, Dante ; Zhou, Tong ; Angermann, Jeffrey E. ; Ferguson, Bradley S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-8098c5b170462436f9aa5d557e32ec3dc2c02838bec68f61dd28088fd1b41d093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>acetates</topic><topic>Acetylation</topic><topic>angiotensin II</topic><topic>Angiotensin II - pharmacology</topic><topic>animal disease models</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Cardiac hypertrophy</topic><topic>Cardiomegaly - drug therapy</topic><topic>Cardiomegaly - metabolism</topic><topic>cardiomyocytes</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Emodin</topic><topic>Emodin - pharmacology</topic><topic>enzyme inhibition</topic><topic>Female</topic><topic>fibrosis</topic><topic>Food bioactives</topic><topic>gene expression</topic><topic>Gene Expression - drug effects</topic><topic>gene expression regulation</topic><topic>HDAC</topic><topic>Heart failure</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylase Inhibitors - pharmacology</topic><topic>Histone Deacetylases - genetics</topic><topic>Histone Deacetylases - metabolism</topic><topic>histones</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>hypertrophy</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>phenylephrine</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rheum - chemistry</topic><topic>rhubarb</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Evans, Levi W.</creatorcontrib><creatorcontrib>Bender, Abigail</creatorcontrib><creatorcontrib>Burnett, Leah</creatorcontrib><creatorcontrib>Godoy, Luis</creatorcontrib><creatorcontrib>Shen, Yi</creatorcontrib><creatorcontrib>Staten, Dante</creatorcontrib><creatorcontrib>Zhou, Tong</creatorcontrib><creatorcontrib>Angermann, Jeffrey E.</creatorcontrib><creatorcontrib>Ferguson, Bradley S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of nutritional biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Evans, Levi W.</au><au>Bender, Abigail</au><au>Burnett, Leah</au><au>Godoy, Luis</au><au>Shen, Yi</au><au>Staten, Dante</au><au>Zhou, Tong</au><au>Angermann, Jeffrey E.</au><au>Ferguson, Bradley S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy</atitle><jtitle>The Journal of nutritional biochemistry</jtitle><addtitle>J Nutr Biochem</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>79</volume><spage>108339</spage><epage>108339</epage><pages>108339-108339</pages><artnum>108339</artnum><issn>0955-2863</issn><eissn>1873-4847</eissn><abstract>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.</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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