Cited by 31Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsCardiomyopathy and Myosin Studies

Effective Top-Down LC/MS+ Method for Assessing Actin Isoforms as a Potential Cardiac Disease Marker

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Chen, Yi-Chen, Ayaz-Guner, Serife, Peng, Ying, Lane, Nicole M., Locher, Matthew R., Kohmoto, Takushi, Larsson, Lars, Moss, Richard L. +1 more·2015·Analytical Chemistry

Abstract

Actin is the major component of the cytoskeleton, playing an essential role in the structure and motility of both muscle and nonmuscle cells. It is highly conserved and encoded by a multigene family. α-Cardiac actin (αCAA) and α-skeletal actin (αSKA), encoded by two different genes, are the primary actin isoforms expressed in striated muscles. The relative expression levels of αSKA and αCAA have been shown to vary between species and under pathological conditions. In particular, an increased αSKA expression is believed to be a programmed response of a diseased heart. Therefore, it is essential to quantify the relative expression of αSKA and αCAA, which remains challenging due to the high degree of sequence similarity between these isoforms (98.9%). Herein, we developed a top-down liquid chromatography/mass spectrometry-based ("LC/MS+") method for the rapid purification and comprehensive analysis of α-actin extracted from muscle tissues. We thoroughly investigated all of the actin isoforms in healthy human cardiac and skeletal muscles. We found that αSKA is the only isoform expressed in skeletal muscle, whereas αCAA and αSKA are coexpressed in cardiac muscle. We then applied our method to quantify the α-actin isoforms in human healthy hearts and failing hearts with dilated cardiomyopathy (DCM). We found that αSKA is augmented in DCM compared with healthy controls, 43.1 ± 0.9% versus 23.7 ± 1.7%, respectively. As demonstrated, top-down LC/MS+ provides an effective and comprehensive method for the purification, quantification, and characterization of α-actin isoforms, enabling assessment of their clinical potential as cardiac disease markers.

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Crossref · 10.1021/acs.analchem.5b01745

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  • In the heart, protein isoform switching and PTMs regulate cardiac contraction and relaxation and contribute to heart failure progression.

    “For example, in the heart, protein isoform switching [141], and PTMs are known to regulate cardiac contraction and relaxation, as well as play a role in the progression of heart failure [61,142,143].”

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  1. [32]Chamot-Rooke J Mikaty G Malosse C Soyer M Dumont A Gault J Imhaus AF Martin P Trellet M Clary G Chafey P Camoin L Nilges M Nassif X Dumenil G Science 2011 331 778 782 21311024
  2. [41]Johnson P Harris CI Perry SV Biochem J 1967 105 361 370 6056634 PMC1198308

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Authors
Chen, Y.-C., Ayaz-Guner, S., Peng, Y., Lane, N. M., Locher, M. R., Kohmoto, T., Larsson, L., Moss, R. L., & Ge, Y.
Affiliations
  • University of Wisconsin–Madison (US)
  • Karolinska Institutet (SE)
Corresponding author
Ge, Ying
Venue
Analytical Chemistry
Published
2015-07-31
Volume
87
Issue
16
Pages
8399-8406
ISSN
  • 0003-2700 (ISSN-L)
  • 1520-6882
OpenAlex
W2417588736
Cited by
31
References
56
Citations by year
2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2
FWCI
1.64
Type
journal article
Language
en
Open access
Locations
  • Analytical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (R01 HL096971, R01 HL109810)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
actin isoforms, alpha-cardiac actin, alpha-skeletal actin, top-down mass spectrometry, dilated cardiomyopathy, cardiac biomarkers, myocardium, skeletal muscle, actin purification
MeSH terms
Actins, Chromatography, Liquid, Heart Diseases, Humans, Myocardium, Reference Standards, Mass Spectrometry, Time Factors, Biomarkers, Protein Isoforms

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