STOREDB:STUDY1038 Mayak Nuclear Workers; proteomics on left ventricle [DOI:10.20348/STOREDB/1038]

Study meta-data


STUDYIDSTOREDB:STUDY1038
CREATEDON2016-04-08 12:16:06
MODIFIEDON2016-04-08 12:16:06
UPLOADEROmid Azimzadeh
DOIDOI:10.20348/STOREDB/1038

Study details


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

STOREDB:DATASET1069 RNAseq [DOI:10.20348/STOREDB/1038/1069]


Created on:2016-06-28 13:03:36
Modified On:2016-06-28 13:03:36
DATASET NAME
RNAseq
DOIDOI:10.20348/STOREDB/1038/1069
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STOREDB:DATASET1066 Mayak LV Label-free quantitative proteomics analysis [DOI:10.20348/STOREDB/1038/1066]


Created on:2016-04-08 12:18:33
Modified On:2016-04-15 10:59:13
DATASET NAME
Mayak LV Label-free quantitative proteomics analysis
DOIDOI: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
STORDB MAYAK Samples discription

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