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

Ranjan Banerjee, Jun He, Carolyn Spaniel, Megan T. Quintana, Zhongjing Wang, James R. Bain, Christopher B. Newgard, Michael J. Muehlbauer, Monte Willis

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)312-322
Number of pages11
JournalMetabolomics
Volume11
Issue number2
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Metabolomics
Fingers
Muscle
Myocardium
Muscles
Metabolism
Taurine
Proteins
Libraries
Metabolome
Biosynthesis
Inositol
Ligases
Metabolites
Ubiquitin
Substrate Specificity
Metabolic Networks and Pathways
Ascorbic Acid
Heart Diseases
Statistical methods

Keywords

  • Cardiac
  • Metabolomics
  • MuRF2
  • MuRF3
  • Muscle Ring Finger-1 (MuRF1)
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes. / Banerjee, Ranjan; He, Jun; Spaniel, Carolyn; Quintana, Megan T.; Wang, Zhongjing; Bain, James R.; Newgard, Christopher B.; Muehlbauer, Michael J.; Willis, Monte.

In: Metabolomics, Vol. 11, No. 2, 01.04.2015, p. 312-322.

Research output: Contribution to journalArticle

Banerjee, Ranjan ; He, Jun ; Spaniel, Carolyn ; Quintana, Megan T. ; Wang, Zhongjing ; Bain, James R. ; Newgard, Christopher B. ; Muehlbauer, Michael J. ; Willis, Monte. / Non-targeted metabolomics analysis of cardiac Muscle Ring Finger-1 (MuRF1), MuRF2, and MuRF3 in vivo reveals novel and redundant metabolic changes. In: Metabolomics. 2015 ; Vol. 11, No. 2. pp. 312-322.
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