Transcription coactivator Eya2 is a critical regulator of physiological hypertrophy
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Seung Hee | - |
dc.contributor.author | Kim, Jooyeon | - |
dc.contributor.author | Ryu, Joo Young | - |
dc.contributor.author | Lee, Suho | - |
dc.contributor.author | Yang, Dong Kwon | - |
dc.contributor.author | Jeong, Dongtak | - |
dc.contributor.author | Kim, Jaetaek | - |
dc.contributor.author | Lee, Sang-Hee | - |
dc.contributor.author | Kim, Jin Man | - |
dc.contributor.author | Hajjar, Roger J. | - |
dc.contributor.author | Park, Woo Jin | - |
dc.date.available | 2019-05-29T07:40:11Z | - |
dc.date.issued | 2012-03 | - |
dc.identifier.issn | 0022-2828 | - |
dc.identifier.issn | 1095-8584 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20473 | - |
dc.description.abstract | Despite its significant clinical implications, physiological hypertrophy remains poorly understood. In this study, the transcription coactivator Eya2 was shown to be up-regulated during physiological hypertrophy. Transgene- or adenovirus-mediated overexpression of Eya2 led to up-regulation of mTOR, a critical mediator of physiological hypertrophy. Luciferase reporter and chromatin immunoprecipitation assays revealed that Eya2 directly binds to and activates mTOR expression. The phosphorylation of mTOR downstream molecules was significantly enhanced in Eya2 transgenic (TG) hearts, implying that the Eya2-mediated induction of mTOR expression leads to an elevated mTOR activity. The transcription factor Six1 was also up-regulated during physiological hypertrophy and formed a complex with Eya2. Luciferase reporter and electrophoretic mobility shift assays revealed that the Eya2-Six1 complex binds to and enhances the expression of mTOR in a synergistic manner. Under pressure overload, Eya2 transgenic hearts developed hypertrophy which exhibited important molecular signatures of physiological hypertrophy, as assessed by gene expression profiling and measurements of expression levels of physiological hypertrophy-related genes by quantitative (q) RT-PCR. Examination of heart sections under electron microscopy revealed that the mitochondrial integrity remained largely intact in Eya2 transgenic mice, but not in wild-type littermates, under pressure overload. This finding was confirmed by measurements of mitochondrial DNA contents and the expression levels of mitochondrial function-related genes by qRT-PCR. These data suggest that Eya2 in a physical complex with Six1 plays a critical role in physiological hypertrophy. The cardioprotective effect of Eya2 appears to be due, at least in part, to its preservation of mitochondrial integrity upon pressure overload. (C) 2011 Elsevier Ltd. All rights reserved. | - |
dc.format.extent | 9 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | - |
dc.title | Transcription coactivator Eya2 is a critical regulator of physiological hypertrophy | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.yjmcc.2011.12.002 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, v.52, no.3, pp 718 - 726 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000301621000023 | - |
dc.identifier.scopusid | 2-s2.0-84862816399 | - |
dc.citation.endPage | 726 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 718 | - |
dc.citation.title | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | - |
dc.citation.volume | 52 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | Physiological cardiac hypertrophy | - |
dc.subject.keywordAuthor | Eyes absent 2 | - |
dc.subject.keywordAuthor | Six1 | - |
dc.subject.keywordAuthor | mTOR | - |
dc.subject.keywordAuthor | Cardiac protection | - |
dc.subject.keywordPlus | INDUCED CARDIAC-HYPERTROPHY | - |
dc.subject.keywordPlus | EYES-ABSENT GENE | - |
dc.subject.keywordPlus | MICROTUBULE DEPOLYMERASE KIF2A | - |
dc.subject.keywordPlus | SIGNALING PATHWAYS | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | HEART-FAILURE | - |
dc.subject.keywordPlus | PROTEIN CDK5 | - |
dc.subject.keywordPlus | DROSOPHILA | - |
dc.subject.keywordPlus | EXERCISE | - |
dc.subject.keywordPlus | CARDIOMYOPATHY | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cardiac & Cardiovascular Systems | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.