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Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes.

Publication ,  Journal Article
Banerjee, R; He, J; Spaniel, C; Quintana, MT; Wang, Z; Bain, J; Newgard, CB; Muehlbauer, MJ; Willis, MS
Published in: Metabolomics
April 2015

The muscle-specific ubiquitin ligases MuRF1, MuRF2, MuRF3 have been reported to have overlapping substrate specificities, interacting with each other as well as proteins involved in metabolism and cardiac function. In the heart, all three MuRF family proteins have proven critical to cardiac responses to ischemia and heart failure. The non-targeted metabolomics analysis of MuRF1-/-, MuRF2-/-, and MuRF3-/- hearts was initiated to investigate the hypothesis that MuRF1, MuRF2, and MuRF3 have a similarly altered metabolome, representing alterations in overlapping metabolic processes. Ventricular tissue was flash frozen and quantitatively analyzed by GC/MS using a library built upon the Fiehn GC/MS Metabolomics RTL Library. Non-targeted metabolomic analysis identified significant differences (via VIP statistical analysis) in taurine, myoinositol, and stearic acid for the three MuRF-/- phenotypes relative to their matched controls. Moreover, pathway enrichment analysis demonstrated that MuRF1-/- had significant changes in metabolite(s) involved in taurine metabolism and primary acid biosynthesis while MuRF2-/- had changes associated with ascorbic acid/aldarate metabolism (via VIP and t-test analysis vs. sibling-matched wildtype controls). By identifying the functional metabolic consequences of MuRF1, MuRF2, and MuRF3 in the intact heart, non-targeted metabolomics analysis discovered common pathways functionally affected by cardiac MuRF family proteins in vivo. These novel metabolomics findings will aid in guiding the molecular studies delineating the mechanisms that MuRF family proteins regulate metabolic pathways. Understanding these mechanism is an important key to understanding MuRF family proteins' protective effects on the heart during cardiac disease.

Duke Scholars

Published In

Metabolomics

DOI

ISSN

1573-3882

Publication Date

April 2015

Volume

11

Issue

2

Start / End Page

312 / 322

Location

United States

Related Subject Headings

  • Analytical Chemistry
  • 3401 Analytical chemistry
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
  • 1103 Clinical Sciences
  • 0601 Biochemistry and Cell Biology
  • 0301 Analytical Chemistry
 

Citation

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Banerjee, R., He, J., Spaniel, C., Quintana, M. T., Wang, Z., Bain, J., … Willis, M. S. (2015). Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes. Metabolomics, 11(2), 312–322. https://doi.org/10.1007/s11306-014-0695-1
Banerjee, Ranjan, Jun He, Carolyn Spaniel, Megan T. Quintana, Zhongjing Wang, James Bain, Christopher B. Newgard, Michael J. Muehlbauer, and Monte S. Willis. “Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes.Metabolomics 11, no. 2 (April 2015): 312–22. https://doi.org/10.1007/s11306-014-0695-1.
Banerjee R, He J, Spaniel C, Quintana MT, Wang Z, Bain J, et al. Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes. Metabolomics. 2015 Apr;11(2):312–22.
Banerjee, Ranjan, et al. “Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes.Metabolomics, vol. 11, no. 2, Apr. 2015, pp. 312–22. Pubmed, doi:10.1007/s11306-014-0695-1.
Banerjee R, He J, Spaniel C, Quintana MT, Wang Z, Bain J, Newgard CB, Muehlbauer MJ, Willis MS. Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes. Metabolomics. 2015 Apr;11(2):312–322.
Journal cover image

Published In

Metabolomics

DOI

ISSN

1573-3882

Publication Date

April 2015

Volume

11

Issue

2

Start / End Page

312 / 322

Location

United States

Related Subject Headings

  • Analytical Chemistry
  • 3401 Analytical chemistry
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
  • 1103 Clinical Sciences
  • 0601 Biochemistry and Cell Biology
  • 0301 Analytical Chemistry