STOREDB:STUDY1040 High-dose ionising radiation affects TGF beta and PPAR alpha signalling pathways 40 weeks after local heart irradiation in C57BL/6J mice [DOI:10.20348/STOREDB/1040]

Study meta-data


STUDYIDSTOREDB:STUDY1040
CREATEDON2016-05-19 15:19:52
MODIFIEDON2016-08-02 13:09:19
UPLOADEROmid Azimzadeh
DOIDOI:10.20348/STOREDB/1040

Study details


STUDY NAME
High-dose ionising radiation affects TGF beta and PPAR alpha signalling pathways 40 weeks after local heart irradiation in C57BL/6J mice
STUDY STATUS
Published: Open access to everyone
DATA SHARING POLICY
CC-Attribution Non-Commercial Share Alike
COUNTRY
Germany
PRINCIPAL INVESTIGATOR
Dr. Omid Azimzadeh
SPECIES
Mus musculus
SIZE OF COHORT
0-999
OUTCOME
Cardiovascular
MELODI RESEARCH PRIORITY
Identification of specific metabolic pathways and tissue biomarkers related to radiation specific tissue responses.
EXPOSURE CONTEXT
Medical
INTERNAL OR EXTERNAL EXPOSURE
External
TYPE OF EXTERNAL EXPOSURE
X-ray
TYPE OF INTERNAL EXPOSURE
Gamma
AGE AT EXPOSURE
Adult
EXPOSURE PATTERN
Acute
DOSE RATE
High
BIOLOGICAL SAMPLE AVAILABLE
No
STUDY DESCRIPTION
Epidemiological data from radiotherapy of thoracic and chest wall tumours show the damaging effect of ionising radiation on heart and vasculature. The long-term impairment of heart function and structure after local high-dose irradiation in mice is associated with systemic inflammatory response, contraction impairment, microvascular damage and cardiac fibrosis. The goal of the present study was to investigate molecular mechanisms involved in this process. C57BL/6J mice received X-ray doses of 8 and 16 Gy locally to the heart at the age of 8 weeks; the control mice were sham-irradiated. Radiation-induced changes in the heart transcriptome and proteome were investigated 40 weeks after the exposure using Illumina Expression Bead and Isotope Coded Protein Label technologies, respectively. The omics data were analysed by bioinformatics tools and validated by immunoblotting. The changes in the irradiated cardiac proteome indicated a perturbation of energy metabolism and its key regulator peroxisome proliferator-activated receptor (PPAR) alpha. Both proteomics and transcriptomics data predicted induction of transforming growth factor (TGF) beta signalling. The predicted mediator role of mitogen-activated protein (MAP) kinase cascade between PPAR alpha and TGF beta signalling pathways was analysed by immunoblotting. This study indicates that both pathways are involved in radiation-induced heart fibrosis, metabolic disordering and impaired contractility. These data are in line with the pathophysiological condition observed in patients that received high radiation doses in thorax.
MEAN DURATION OF FOLLOW-UP (WEEKS)
40

STOREDB:DATASET1068 proteomics and trabscriptomics on 40 weeks after local heart irradiation in C57BL/6J mice [DOI:10.20348/STOREDB/1040/1068]


Created on:2016-05-19 15:20:28
Modified On:2016-08-02 12:21:35
DATASET NAME
proteomics and trabscriptomics on 40 weeks after local heart irradiation in C57BL/6J mice
DOIDOI:10.20348/STOREDB/1040/1068
DATASET DESCRIPTION
They are MS/MS data analysed separately on a LTQ OrbitrapXL (Thermo Fisher Scientific) coupled to Ultimate 3000 nano-HPLC (Dionex). The raw files of the individual measurements were loaded to the Progenesis QI software and analysed. Briefly, peptide features in the individual runs were aligned in order to reach a maximum overlay of at least 87%. After feature detection, the singly charged features and features with charges higher than +7 were excluded. The samples were grouped according to the radiation dose as described above. Protein identification was performed using the Mascot search engine (Matrix Science, version 2.5.1) in the Ensembl mouse database (release 75, 23354020 residues, 51771 sequences). The following search parameters were used: 10 ppm peptide mass tolerance and 0.6 Da fragment mass tolerance, one missed cleavage was allowed, carbamidomethylation (C) was set as fixed modification, and oxidation (M) and deamidation (N, Q) were allowed as variable modifications. Search results were reimported into the Progenesis QI software and the resulting summed normalised abundances of the unique peptides for every single protein were used for the calculation of abundance ratios and statistical analysis (Studentís t-test). For final quantifications, proteins with ratios greater than 1.30-fold or less than 0.77-fold (t-test; p< 0.05) were defined as being significantly differentially expressed. The FDR (q value) calculation was used to adjust p-values.
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