Summary of Study ST000429

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000333. The data can be accessed directly via it's Project DOI: 10.21228/M88885 This work is supported by NIH grant, U2C- DK119886.

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Study IDST000429
Study TitleTargeted metabolomics of MuRF1 overexpressing cardiomyocytes compared to their wildtype controls (part I)
Study TypeTargeted metabolomic analysis
Study SummaryThe transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1−/− hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1's targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.
Institute
University of North Carolina at Chapel Hill
DepartmentMcAllister Heart Institute, Department of Internal Medicine
LaboratoryMultiple Centers
Last NameWillis
First NameMonte
Address111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Emailmonte_willis@med.unc.edu
Phone919-360-7599
Submit Date2016-07-05
Analysis Type DetailGC-MS
Release Date2016-09-23
Release Version1
Monte Willis Monte Willis
https://dx.doi.org/10.21228/M88885
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Treatment:

Treatment ID:TR000464
Treatment Summary:N/A
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