{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:43:08Z","timestamp":1793032988693,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T00:00:00Z","timestamp":1537056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2019,3]]},"abstract":"Summary<\/jats:title>Histone deacetylases (HDAC<\/jats:styled-content>s) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II<\/jats:styled-content> (4, 5, 6, 7, 9 and 10), class III<\/jats:styled-content> (sirtuin family) and class IV<\/jats:styled-content> (HDAC<\/jats:styled-content>11). HDAC<\/jats:styled-content> inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC<\/jats:styled-content>1) signaling. HDAC<\/jats:styled-content> inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC<\/jats:styled-content>2), an mTORC<\/jats:styled-content>1 inhibitor. However, the molecular mechanism underlying HDAC<\/jats:styled-content> inhibitor\u2010mediated upregulation of TSC<\/jats:styled-content>2 is unclear. We hypothesized that an HDAC<\/jats:styled-content> inhibitor, CG<\/jats:styled-content>200745 (CG<\/jats:styled-content>), ameliorates cardiac hypertrophy through the inhibition of mTORC<\/jats:styled-content>1 signaling by upregulating of the CCAAT<\/jats:styled-content>\/enhancer\u2010binding protein\u2010\u03b2 (C\/EBP<\/jats:styled-content>\u2010\u03b2)\/TSC<\/jats:styled-content>2 pathway. To establish a cardiac hypertrophy model, deoxycorticosterone acetate (DOCA<\/jats:styled-content>, 40 mg\/kg\/wk) was subcutaneously injected for 4\u00a0weeks into Sprague\u2010Dawley rats. All rats were unilaterally nephrectomized and had free access to drinking water containing 1% NaCl with or without CG<\/jats:styled-content> of different concentrations. The expression level of TSC<\/jats:styled-content>2 and C\/EBP<\/jats:styled-content>\u2010\u03b2 was measured by quantitative real\u2010time PCR<\/jats:styled-content> (qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>) and western blot analysis. Acetylation of C\/EBP<\/jats:styled-content>\u2010\u03b2 was analyzed by immunoprecipitation. The recruitment of C\/EBP<\/jats:styled-content>\u2010\u03b2 and polymerase II<\/jats:styled-content> (Pol II<\/jats:styled-content>) on TSC<\/jats:styled-content>2 promoter region was analyzed by chromatin immunoprecipitation (ChIP<\/jats:styled-content>). CG<\/jats:styled-content> treatment increased the expression of TSC<\/jats:styled-content>2. In addition, CG<\/jats:styled-content> treated rats showed an increased in the expression and acetylation of C\/EBP<\/jats:styled-content>\u2010\u03b2, owing to the increase in the recruitment of C\/EBP<\/jats:styled-content>\u2010\u03b2 and Pol II<\/jats:styled-content> at Tsc2<\/jats:italic> gene promoter. Thus, CG<\/jats:styled-content> ameliorates cardiac hypertrophy through the inhibition of mTORC<\/jats:styled-content>1 signaling via upregulation of the C\/EBP<\/jats:styled-content>\u2010\u03b2\/TSC<\/jats:styled-content>2 pathway in DOCA<\/jats:styled-content>\u2010induced hypertensive rats.<\/jats:p>","DOI":"10.1111\/1440-1681.13022","type":"journal-article","created":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T21:44:08Z","timestamp":1534110248000},"page":"226-236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Upregulation of C\/EBP<\/scp>\u03b2 and TSC<\/scp>2 by an HDAC<\/scp> inhibitor CG<\/scp>200745 protects heart from DOCA<\/scp>\u2010induced hypertrophy"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-1631","authenticated-orcid":false,"given":"Eunjo","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cardiovascular Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cell and Matrix Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"BK21 Plus KNU Biomedical Convergence program Department of Biomedical Science School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae\u2010Ahm","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cardiovascular Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cell and Matrix Research Institute School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cardiovascular Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cell and Matrix Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"BK21 Plus KNU Biomedical Convergence program Department of Biomedical Science School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga young","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Min","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cardiovascular Research Institute School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Jik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery Kyungpook National University Hospital Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery Kyungpook National University Hospital Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hup","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Public Health Medical Service Kyungpook National University Hospital Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joong Myung","family":"Cho","sequence":"additional","affiliation":[{"name":"CrystalGenomics, Inc. Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inkyeom","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cardiovascular Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"Cell and Matrix Research Institute School of Medicine Kyungpook National University Daegu Korea"},{"name":"BK21 Plus KNU Biomedical Convergence program Department of Biomedical Science School of Medicine Kyungpook National University Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra072139"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001878"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.013894"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.02.006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4068\/cmj.2016.52.1.1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010611-134712"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2016.20.5.477"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11861"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.11.1422"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2011.09.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq570"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.10.1069"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aad5736"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.12.019"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0223-2"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.036"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.619957"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.02.058"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.211540"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001327"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000350148"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.096974"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-015-0262-2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302022"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21197"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080281"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06286.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511451200"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2008.03.009"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607378104"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1565"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1440-1681.13022","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:03:47Z","timestamp":1694696627000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.13022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,16]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/1440-1681.13022"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.13022","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,16]]},"assertion":[{"value":"2018-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}