STOREDB:STUDY1053 A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers [DOI:10.20348/STOREDB/1053]

Study meta-data


STUDYIDSTOREDB:STUDY1053
CREATEDON2016-10-07 12:51:46
MODIFIEDON2017-08-08 11:57:54
UPLOADERPaul Schofield
DOIDOI:10.20348/STOREDB/1053

Study details


STUDY NAME
A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers
STUDY STATUS
Published: Open access to everyone
DATA SHARING POLICY
CC-Attribution Share Alike
COUNTRY
Germany
PRINCIPAL INVESTIGATOR
Soile Tapio
SPECIES
Homo sapiens
SIZE OF COHORT
0-999
OUTCOME
Cardiovascular
RADONORM RESEARCH PRIORITY
Identification, development and validation of biomarkers for radiation-induced health (cancer and non-cancer) effects through sound epidemiological studies
EXPOSURE CONTEXT
Occupational
INTERNAL OR EXTERNAL EXPOSURE
Internal
TYPE OF EXTERNAL EXPOSURE
gamma
TYPE OF INTERNAL EXPOSURE
alpha
AGE AT EXPOSURE
Adult
EXPOSURE PATTERN
Protracted
DOSE RATE
Low
BIOLOGICAL SAMPLE AVAILABLE
No
STUDY DESCRIPTION
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. 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, 100500 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. 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.
PUBMED ID
27391067

STOREDB:DATASET1139 Human Patients Mapping Reads [DOI:10.20348/STOREDB/1053/1139]


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DATASET NAME
Human Patients Mapping Reads
DOIDOI:10.20348/STOREDB/1053/1139
DATASET DESCRIPTION
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STOREDB:DATASET1091 Human Patients raw data [DOI:10.20348/STOREDB/1053/1091]


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DATASET NAME
Human Patients raw data
DOIDOI:10.20348/STOREDB/1053/1091
DATASET DESCRIPTION
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STOREDB:DATASET1090 Patient Comparisons/Analysis [DOI:10.20348/STOREDB/1053/1090]


Created on:2016-10-07 13:07:33
Modified On:2016-10-07 13:07:33
DATASET NAME
Patient Comparisons/Analysis
DOIDOI:10.20348/STOREDB/1053/1090
DATASET DESCRIPTION
Principal component analysis/Boxplots/Comparison data
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STOREDB:DATASET1089 Sequencing Quality Control [DOI:10.20348/STOREDB/1053/1089]


Created on:2016-10-07 13:04:32
Modified On:2016-10-07 13:04:32
DATASET NAME
Sequencing Quality Control
DOIDOI:10.20348/STOREDB/1053/1089
DATASET DESCRIPTION
Quality control data for RNAseq
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STOREDB:DATASET1088 Library Quality Control [DOI:10.20348/STOREDB/1053/1088]


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Modified On:2016-10-07 13:02:34
DATASET NAME
Library Quality Control
DOIDOI:10.20348/STOREDB/1053/1088
DATASET DESCRIPTION
Quality control data
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STOREDB:DATASET1087 Gene Expression Tables [DOI:10.20348/STOREDB/1053/1087]


Created on:2016-10-07 12:56:03
Modified On:2016-10-07 12:56:03
DATASET NAME
Gene Expression Tables
DOIDOI:10.20348/STOREDB/1053/1087
DATASET DESCRIPTION
Summary gene expression tables ( Excel file) for individuals 1-5.
Sample 8 in RNAseq is number 16 in Mayak manuscript
Sample 9 in RNAseq is number 26 in Mayak manuscript
Sample 12 in RNAseq is number 31 in Mayak manuscript (bad RNA quality)
Sample 13 in RNAseq is number 37 in Mayak manuscript
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