| STUDYID | STOREDB:STUDY1038 |
|---|---|
| CREATEDON | 2016-04-08 12:16:06 |
| MODIFIEDON | 2016-04-08 12:16:06 |
| UPLOADER | Omid Azimzadeh |
| DOI | DOI:10.20348/STOREDB/1038 |
| STUDY NAME | ||
|---|---|---|
| Mayak Nuclear Workers; proteomics on left ventricle | ||
| STUDY STATUS | ||
| Published: Open access to everyone | ||
| DATA SHARING POLICY | ||
| CC-Attribution Non-Commercial | ||
| COUNTRY | ||
| Germany | ||
| PRINCIPAL INVESTIGATOR | ||
| Dr. Soile Tapio | ||
| SPECIES | ||
| Homo sapiens | ||
| SIZE OF COHORT | ||
| 0-999 | ||
| OUTCOME | ||
| Cardiovascular | ||
| RADONORM RESEARCH PRIORITY | ||
| Identification of specific metabolic pathways and tissue biomarkers related to radiation specific tissue responses. | ||
| EXPOSURE CONTEXT | ||
| Occupational | ||
| INTERNAL OR EXTERNAL EXPOSURE | ||
| External | ||
| TYPE OF EXTERNAL EXPOSURE | ||
| X-ray | ||
| TYPE OF INTERNAL EXPOSURE | ||
| Gamma | ||
| AGE AT EXPOSURE | ||
| Adult | ||
| EXPOSURE PATTERN | ||
| Protracted | ||
| DOSE RATE | ||
| Low | ||
| BIOLOGICAL SAMPLE AVAILABLE | ||
| Yes | ||
| STUDY DESCRIPTION | ||
| A Dose-dependent Perturbation in Cardiac Energy Metabolism is Linked to Radiation-induced Ischemic Heart Disease in Mayak Nuclear Workers
Background - Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans. Methods and Results – The cardiac proteome response to irradiation was analysed in Mayak workers who were exposed only to external doses of gamma rays. All participants were diagnosed during their lifetime with IHD that also was the cause of death. Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, <100 mGy, 100 - 500 mGy, and >500 mGy). The groups could be separated using principal component analysis based on all proteomics features. Proteome profiling showed a dose-dependent increase in the number of downregulated mitochondrial and structural proteins. Both proteomics and immunoblotting showed decreased expression of several oxidative stress responsive proteins in the irradiated hearts. The phosphorylation of transcription factor PPAR alpha was increased in a dose-dependent manner, which is indicative of a reduction in transcriptional activity with increased radiation dose. Conclusions - These data suggest that chronic external radiation enhances the risk for IHD by inhibiting PPAR alpha and altering the expression of mitochondrial, structural, and antioxidant components of the heart. | ||
| MEAN DURATION OF FOLLOW-UP (WEEKS) | ||
| 150 | ||
| DATASET NAME | ||
|---|---|---|
| RNAseq | ||
| DOI | DOI:10.20348/STOREDB/1038/1069 | |
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| DATASET NAME | ||
|---|---|---|
| Mayak LV Label-free quantitative proteomics analysis | ||
| DOI | DOI:10.20348/STOREDB/1038/1066 | |
| DATASET DESCRIPTION | ||
| The cardiac left ventricle was collected at autopsy and immediately frozen. Heart tissues from 28 individuals were allocated between four dose groups as follows: 3 individuals to the control group (0 Gy), 6 to the dose group <100 mGy, 10 individuals to the group receiving doses between 100 - 500 mGy, and 10 individuals to the dose group >500 mGy.
Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, <100 mGy, 100 - 500 mGy, and >500 mGy). The cardiac left ventricle was collected at autopsy and immediately frozen. Heart tissues from 28 individuals were allocated between four dose groups as follows: 3 individuals to the control group (0 Gy), 6 to the dose group <100 mGy, 10 individuals to the group receiving doses between 100 - 500 mGy, and 10 individuals to the dose group >500 mGy (Supplementary Table S10). The smoking status and index, alcohol consumption and body mass index of each individual is indicated in Supplementary Table S10. Sample numbers appear for each MS MS file at the end of MS ID as following: AZO7404A4MA3__004-38 for individual sample number 38 | ||
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