Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MuRF1 regulation of Fenofibrateâs induction of spontaneous cardiac hypertrophy in vivo.

ABSTRACT: MuRF1 -/- w/ Fenofibrate treatment leads to the reduction of proteolytic and fibrolytic enzymes, increasing hypertrophy Four strain-matched groups of 3-8 week old mice were investigated: 1) MuRF1 -/- Fenofibrate feed; 2) MuRF1 -/- chow feed; 3) MuRF1 +/+ Fenofibrate feed; 4) MuRF1 +/+ chow feed at two time points: 1) 3 weeks; 2) 8 Weeks Biological replicates: Two to three per condition. Hearts harvested. One replicate per array.

ORGANISM(S): Mus musculus

SUBMITTER: Monte Willis

PROVIDER: E-GEOD-68480 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Fenofibrate unexpectedly induces cardiac hypertrophy in mice lacking MuRF1.

Parry Traci L TL Desai Gopal G Schisler Jonathan C JC Li Luge L Quintana Megan T MT Stanley Natalie N Lockyer Pamela P Patterson Cam C Willis Monte S MS

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 20151029 2

The muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) is critical in regulating both pathological and physiological cardiac hypertrophy in vivo. Previous work from our group has identified MuRF1's ability to inhibit serum response factor and insulin-like growth factor-1 signaling pathways (via targeted inhibition of cJun as underlying mechanisms). More recently, we have identified that MuRF1 inhibits fatty acid metabolism by targeting peroxisome proliferator-activated receptor alpha ...[more]

PMID: 26764147

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Project description:Muscle ring finger-1 (MuRF1) is a muscle-specific protein implicated in the regulation of cardiac myocyte size and contractility. MuRF2, a closely related family member, redundantly interacts with protein substrates, and hetero-dimerizes with MuRF1. Mice lacking either MuRF1 or MuRF2 are phenotypically normal whereas mice lacking both proteins develop a spontaneous cardiac and skeletal muscle hypertrophy indicating cooperative control of muscle mass by MuRF1 and MuRF2. In order to identify the role that MuRF1 plays in regulating cardiac hypertrophy in vivo, we created transgenic mice expressing increased amounts of cardiac MuRF1. Adult MuRF1 transgenic (Tg+) hearts exhibited a non-progressive thinning of the left ventricular wall and a concomitant decrease in cardiac function. Experimental induction of cardiac hypertrophy by trans-aortic constriction (TAC) induced rapid failure of MuRF1 Tg+ hearts. Microarray analysis identified that the levels of genes associated with metabolism (and in particular mitochondrial processes) were significantly altered in MuRF1 Tg+ hearts, both at baseline and during the development of cardiac hypertrophy. Surprisingly, ATP levels in MuRF1 Tg+ mice did not differ from wild type mice despite the depressed contractility following TAC. To explain this discrepancy between the ongoing heart failure and maintained ATP levels in MuRF1 Tg+ hearts, we compared the level and activity of creatine kinase (CK) between wild type and MuRF1 Tg+ hearts. Although mCK and CK-M/B protein levels were unaffected in MuRF1 Tg+ hearts, total CK activity was significantly inhibited. We conclude that MuRF1’s inhibition of CK activity leads to increased susceptibility to heart failure following TAC, demonstrating for the first time that MuRF1 regulates cardiac energetics in vivo. Keywords: Genetic modification, physiological manipulation. Three-condition experiment, MuRF1 Tg+ vs. WT mice. Biological replicates: 4 WT baseline, 3 MuRF1 Tg+ baseline, cardiac overpressure hypertrophy induced by trans-aortic banding at 1 week (3 WT, 3 MurF Tg) and 4 weeks (3 WT, 3 MurF Tg), hearts harvested. One replicate per array.

Dataset Information

MuRF1 regulation of Fenofibrateâs induction of spontaneous cardiac hypertrophy in vivo.

Publications

Fenofibrate unexpectedly induces cardiac hypertrophy in mice lacking MuRF1.

Similar Datasets

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MuRF1 regulation of Fenofibrateâs induction of spontaneous cardiac hypertrophy in vivo.