Document Detail


The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload.
MedLine Citation:
PMID:  17618854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Cell metabolism     Volume:  6     ISSN:  1550-4131     ISO Abbreviation:  Cell Metab.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-09     Completed Date:  2007-08-16     Revised Date:  2011-05-13    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25-37     Citation Subset:  IM    
Affiliation:
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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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