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Quantitative Analysis of Chromatin Proteomes in Disease
Published on: December 28, 2012
Selenium protein identification and profiling by mass spectrometry: A tool to assess progression of cardiomyopathy in
Colleen E Bryan1, Gregory D Bossart2, Steven J Christopher1
1Chemical Sciences Division, National Institute of Standards and Technology, Hollings Marine Laboratory, 331 Fort Johnson Road, Charleston, SC 29412, USA.
Insights
Selenium protein profiles differ in pygmy sperm whales with cardiomyopathy. Metallothioneins, associated with selenium, were more abundant in whales with heart disease, suggesting a link between selenium and cardiomyopathy.
Area of Science:
- Marine Mammal Health
- Toxicology
- Biochemistry
Background:
- Non-ischemic cardiomyopathy is a significant cause of heart failure and sudden death in humans.
- Pygmy sperm whales (Kogia breviceps) exhibit the highest known prevalence of cardiomyopathy, affecting over half of individuals.
- Potential causes include genetics, infections, contaminants, biotoxins, and nutritional deficiencies like selenium.
Purpose of the Study:
- To investigate the role of selenium (Se) proteins in the development of cardiomyopathy in Kogia breviceps.
- To explore the presence and abundance of Se proteins in relation to cardiomyopathy in whale tissues.
- To determine if Se protein profiles can differentiate between healthy and affected individuals.
Main Methods:
- Selenium proteins were analyzed using multi-dimension liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS).
- Protein identification was performed via liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS).
- Selenium protein profiles were examined in liver (n=30) and heart tissue (n=5) using SEC/UV/ICP-MS detection.
Main Results:
- Selenium protein profiles varied in presence and intensity between whales with and without cardiomyopathy.
- Metallothioneins, a class of proteins associated with Se, were found in greater abundance in whales with cardiomyopathy.
- SEC/ICP-MS successfully differentiated Se protein patterns related to cardiomyopathy stages in K. breviceps.
Conclusions:
- Selenium protein profiling is a valuable tool for studying cardiomyopathy in Kogia breviceps.
- Differences in Se protein abundance, particularly metallothioneins, are associated with cardiomyopathy in this species.
- This approach may be applicable to other species for investigating Se's role in heart disease.
Abstract:
Non-ischemic cardiomyopathy is a leading cause of congestive heart failure and sudden cardiac death in humans and in some cases the etiology of cardiomyopathy can include the downstream effects of an essential element deficiency. Of all mammal species, pygmy sperm whales (Kogia breviceps) present the greatest known prevalence of cardiomyopathy with more than half of examined individuals indicating the presence of cardiomyopathy from gross and histo-pathology. Several factors such as genetics, infectious agents, contaminants, biotoxins, and inappropriate dietary intake (vitamins, selenium, mercury, and pro-oxidants), may contribute to the development of idiopathic cardiomyopathy in K. breviceps. Due to the important role Se can play in antioxidant biochemistry and protein formation, Se protein presence and relative abundance were explored in cardiomyopathy related cases. Selenium proteins were separated and detected by multi-dimension liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS), Se protein identification was performed by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS), and Se protein profiles were examined in liver (n=30) and heart tissue (n=5) by SEC/UV/ICP-MS detection. Data collected on selenium proteins was evaluated in the context of individual animal trace element concentration, life history, and histological information. Selenium containing protein peak profiles varied in presence and intensity between animals with no pathological findings of cardiomyopathy and animals exhibiting evidence of cardiomyopathy. In particular, one class of proteins, metallothioneins, was found to be associated with Se and was in greater abundance in animals with cardiomyopathy than those with no pathological findings. Profiling Se species with SEC/ICP-MS proved to be a useful tool to identify Se protein pattern differences between heart disease stages in K. breviceps and an approach similar to this may be applied to other species to study Se protein associations with cardiomyopathy.
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