Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains

Aldrin V Gomes, Katarzyna Kazmierczak, Jenice X. Cheah, Jennifer E. Gilda, Chen Ching Yuan, Zhiqun Zhou, Danuta Szczesna-Cordary

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In this study we aimed to provide an in-depth proteomic analysis of differentially expressed proteins in the hearts of transgenic mouse models of pathological and physiological cardiac hypertrophy using tandem mass tag labeling and liquid chromatography tandem mass spectrometry. The Δ43 mouse model, expressing the 43-amino-acid N-terminally truncated myosin essential light chain (ELC) served as a tool to study the mechanisms of physiological cardiac remodeling, while the pathological hypertrophy was investigated in A57G (Alanine 57 → Glycine) ELC mice. The results showed that 30 proteins were differentially expressed in Δ43 versus A57G hearts as determined by multiple pair comparisons of the mutant versus wild-type (WT) samples with P <0.05. The A57G hearts showed differential expression of nine mitochondrial proteins involved in metabolic processes compared to four proteins for ∆43 hearts when both mutants were compared to WT hearts. Comparisons between ∆43 and A57G hearts showed an upregulation of three metabolically important mitochondrial proteins but downregulation of nine proteins in ∆43 hearts. The physiological model of cardiac hypertrophy (∆43) showed no changes in the levels of Ca2+-binding proteins relative to WT, while the pathologic model (A57G) showed the upregulation of three Ca2+-binding proteins, including sarcalumenin. Unique differences in chaperone and fatty acid metabolism proteins were also observed in Δ43 versus A57G hearts. The proteomics data support the results from functional studies performed previously on both animal models of cardiac hypertrophy and suggest that the A57G- and not ∆43- mediated alterations in fatty acid metabolism and Ca2+ homeostasis may contribute to pathological cardiac remodeling in A57G hearts.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalJournal of Muscle Research and Cell Motility
DOIs
StateAccepted/In press - Dec 14 2015

Fingerprint

Myosin Light Chains
Proteomics
Alanine
Glycine
Animals
Animal Models
Mutation
Cardiomegaly
Mitochondrial Proteins
Proteins
Metabolism
Carrier Proteins
Up-Regulation
Fatty Acids
Physiological models
Liquid chromatography
Tandem Mass Spectrometry
Liquid Chromatography
Labeling
Hypertrophy

Keywords

  • Molecular proteomics
  • Myosin ELC
  • Pathological hypertrophy
  • Transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biochemistry

Cite this

Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains. / Gomes, Aldrin V; Kazmierczak, Katarzyna; Cheah, Jenice X.; Gilda, Jennifer E.; Yuan, Chen Ching; Zhou, Zhiqun; Szczesna-Cordary, Danuta.

In: Journal of Muscle Research and Cell Motility, 14.12.2015, p. 1-15.

Research output: Contribution to journalArticle

Gomes, Aldrin V ; Kazmierczak, Katarzyna ; Cheah, Jenice X. ; Gilda, Jennifer E. ; Yuan, Chen Ching ; Zhou, Zhiqun ; Szczesna-Cordary, Danuta. / Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains. In: Journal of Muscle Research and Cell Motility. 2015 ; pp. 1-15.
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