Document Detail


ATF6 is important under both pathological and physiological states in the heart.
MedLine Citation:
PMID:  20380836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accumulation of unfolded proteins in the endoplasmic reticulum (ER) evokes the ER stress response, including activating transcription factor 6 (ATF6), a key transcriptional activator to maintain cellular homeostasis. The ER stress has recently been reported to cause various diseases, but the role of ATF6 in the heart remains unknown. We clarified the role of ATF6 in the heart. The ATF6 activity was increased in the murine heart after myocardial infarction (MI). Treatment of mice with 4-(2-aminoethyl) benzenesulfonyl fluoride, an inhibitor of ATF6, further reduced cardiac function and increased the mortality rate at 14days after MI. Pharmacological inhibition of ATF6 induced dilatation of left ventricle and depression of cardiac function even in sham-operated murine hearts. The transgenic mice that expressed dominant negative mutant of ATF6 showed larger left ventricular dimension and reduced fractional shortening compared with wild-type littermates, resulting in death of heart failure at approximately 8weeks of age. In contrast, cardiac function after MI was better in transgenic mice that expressed constitutively active mutant of ATF6, compared with wild-type littermates. These results suggest that activation of the ER stress response factor ATF6 plays a critical role in not only protecting hearts under the pathological state but also maintaining cardiac function under the physiological state.
Authors:
Hauhiro Toko; Hidehisa Takahashi; Yosuke Kayama; Sho Okada; Tohru Minamino; Fumio Terasaki; Yasushi Kitaura; Issei Komuro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-07
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  49     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-09-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  113-20     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
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MeSH Terms
Descriptor/Qualifier:
Activating Transcription Factor 6 / metabolism*
Animals
Endoplasmic Reticulum / metabolism
Female
Heart / physiology*
Heart Ventricles / metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Inbred Strains
Mice, Transgenic
Myocardial Infarction / metabolism
Chemical
Reg. No./Substance:
0/Activating Transcription Factor 6

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