The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload - PubMed (original) (raw)
The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload
Janice M Huss et al. Cell Metab. 2007 Jul.
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Abstract
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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- P60 DK20579/DK/NIDDK NIH HHS/United States
- P30 DK056341/DK/NIDDK NIH HHS/United States
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- P30 DK056341-06/DK/NIDDK NIH HHS/United States
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- R01 DK074700/DK/NIDDK NIH HHS/United States
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