Effective Top-Down LC/MS+ Method for Assessing Actin Isoforms as a Potential Cardiac Disease Marker Article Swipe
Yi‐Chen Chen
,
Şerife Ayaz‐Güner
,
Ying Peng
,
Nicole Lane
,
Matthew R. Locher
,
Takushi Kohmoto
,
Lars Larsson
,
Richard L. Moss
,
Ying Ge
·
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1021/acs.analchem.5b01745
YOU?
·
· 2015
· Open Access
·
· DOI: https://doi.org/10.1021/acs.analchem.5b01745
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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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acs.analchem.5b01745
- OA Status
- green
- Cited By
- 31
- References
- 56
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2417588736
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2417588736Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1021/acs.analchem.5b01745Digital Object Identifier
- Title
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Effective Top-Down LC/MS+ Method for Assessing Actin Isoforms as a Potential Cardiac Disease MarkerWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2015Year of publication
- Publication date
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2015-07-19Full publication date if available
- Authors
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Yi‐Chen Chen, Şerife Ayaz‐Güner, Ying Peng, Nicole Lane, Matthew R. Locher, Takushi Kohmoto, Lars Larsson, Richard L. Moss, Ying GeList of authors in order
- Landing page
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https://doi.org/10.1021/acs.analchem.5b01745Publisher landing page
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://doi.org/10.1021/acs.analchem.5b01745Direct OA link when available
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Chemistry, Gene isoform, Actin, Chromatography, Computational biology, Biochemistry, Gene, BiologyTop concepts (fields/topics) attached by OpenAlex
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31Total citation count in OpenAlex
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2025: 1, 2024: 7, 2023: 3, 2021: 4, 2020: 2Per-year citation counts (last 5 years)
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56Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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