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Chronic Occupational Exposure to Ionizing Radiation Induces Alterations in the Structure and Metabolism of the Heart: A Proteomic Analysis of Human Formalin-Fixed Paraffin-Embedded (FFPE) Cardiac Tissue.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Sep 17; Vol. 21 (18). Date of Electronic Publication: 2020 Sep 17. - Publication Year :
- 2020
-
Abstract
- Epidemiological studies on workers employed at the Mayak plutonium enrichment plant have demonstrated an association between external gamma ray exposure and an elevated risk of ischemic heart disease (IHD). In a previous study using fresh-frozen post mortem samples of the cardiac left ventricle of Mayak workers and non-irradiated controls, we observed radiation-induced alterations in the heart proteome, mainly downregulation of mitochondrial and structural proteins. As the control group available at that time was younger than the irradiated group, we could not exclude age as a confounding factor. To address this issue, we have now expanded our study to investigate additional samples using archival formalin-fixed paraffin-embedded (FFPE) tissue. Importantly, the control group studied here is older than the occupationally exposed (>500 mGy) group. Label-free quantitative proteomics analysis showed that proteins involved in the lipid metabolism, sirtuin signaling, mitochondrial function, cytoskeletal organization, and antioxidant defense were the most affected. A histopathological analysis elucidated large foci of fibrotic tissue, myocardial lipomatosis and lymphocytic infiltrations in the irradiated samples. These data highlight the suitability of FFPE material for proteomics analysis. The study confirms the previous results emphasizing the role of adverse metabolic changes in the radiation-associated IHD. Most importantly, it excludes age at the time of death as a confounding factor.
- Subjects :
- Chromatography, Liquid
Cytoskeleton metabolism
Cytoskeleton radiation effects
Formaldehyde chemistry
Humans
Lipid Metabolism radiation effects
Male
Mitochondria metabolism
Mitochondria radiation effects
Myocardial Ischemia epidemiology
Myocardial Ischemia etiology
Myocardial Ischemia pathology
Occupational Exposure
Paraffin Embedding
Principal Component Analysis
Protein Interaction Maps
Proteomics methods
Radiation, Ionizing
Signal Transduction radiation effects
Sirtuins metabolism
Tandem Mass Spectrometry
Tissue Fixation
Myocardial Ischemia metabolism
Plutonium adverse effects
Proteome metabolism
Proteome radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32957660
- Full Text :
- https://doi.org/10.3390/ijms21186832