| The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload. | |
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MedLine Citation:
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PMID: 17618854 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Downregulation and functional deactivation of the transcriptional coactivator PGC-1alpha has been implicated in heart failure pathogenesis. We hypothesized that the estrogen-related receptor alpha (ERRalpha), which recruits PGC-1alpha to metabolic target genes in heart, exerts protective effects in the context of stressors known to cause heart failure. ERRalpha(-/-) mice subjected to left ventricular (LV) pressure overload developed signatures of heart failure including chamber dilatation and reduced LV fractional shortening. (31)P-NMR studies revealed abnormal phosphocreatine depletion in ERRalpha(-/-) hearts subjected to hemodynamic stress, indicative of a defect in ATP reserve. Mitochondrial respiration studies demonstrated reduced maximal ATP synthesis rates in ERRalpha(-/-) hearts. Cardiac ERRalpha target genes involved in energy substrate oxidation, ATP synthesis, and phosphate transfer were downregulated in ERRalpha(-/-) mice at baseline or with pressure overload. These results demonstrate that the nuclear receptor ERRalpha is required for the adaptive bioenergetic response to hemodynamic stressors known to cause heart failure. |
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Authors:
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Janice M Huss; Ken-ichi Imahashi; Catherine R Dufour; Carla J Weinheimer; Michael Courtois; Atilla Kovacs; Vincent Giguère; Elizabeth Murphy; Daniel P Kelly |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Cell metabolism Volume: 6 ISSN: 1550-4131 ISO Abbreviation: Cell Metab. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-09 Completed Date: 2007-08-16 Revised Date: 2011-05-13 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 25-37 Citation Subset: IM |
Affiliation:
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Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological Adenosine Triphosphate / metabolism Animals Animals, Newborn Biological Markers / metabolism Blood Pressure Cardiac Output, Low Cardiomegaly / physiopathology Energy Metabolism Female Gene Expression Profiling Heart / embryology, physiopathology* Magnetic Resonance Spectroscopy Male Mice Mice, Inbred C57BL Mice, Knockout Muscle Contraction / physiology Myocytes, Cardiac / cytology, physiology Oligonucleotide Array Sequence Analysis RNA, Messenger / genetics, metabolism Receptors, Estrogen / physiology* Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / genetics, metabolism Ventricular Pressure / physiology* Ventricular Remodeling / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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K01 DK063051/DK/NIDDK NIH HHS; P30 DK056341-06/DK/NIDDK NIH HHS; P30 DK056341-07/DK/NIDDK NIH HHS; P60 DK20579/DK/NIDDK NIH HHS; R01 DK074700-04/DK/NIDDK NIH HHS; R01 HL058493/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/ERRalpha estrogen-related receptor; 0/RNA, Messenger; 0/Receptors, Estrogen; 0/Transcription Factors; 0/peroxisome-proliferator-activated receptor-gamma coactivator-1; 56-65-5/Adenosine Triphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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