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Azimzadeh, O. ; Sievert, W.* ; Sarioglu, H. ; Yentrapalli, R. ; Barjaktarovic, Z. ; Sriharshan, A. ; Ueffing, M. ; Janik, D. ; Aichler, M. ; Atkinson, M.J. ; Multhoff, G.* ; Tapio, S.

PPAR alpha: A novel radiation target in locally exposed Mus musculus heart revealed by quantitative proteomics.

J. Proteome Res. 12, 2700-2714 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Radiation exposure of the thorax is associated with a markedly increased risk of cardiac morbidity and mortality with a latency period of decades. Although many studies have confirmed the damaging effect of ionizing radiation on the myocardium and cardiac endothelial structure and function, the molecular mechanism behind this damage is not yet elucidated. Peroxisome proliferator-activated receptor alpha (PPAR alpha), a transcriptional regulator of lipid metabolism in heart tissue, has recently received great attention in the development of cardiovascular disease. The goal of this study was to investigate radiation-induced cardiac damage in general and the role of PPAR alpha in this process in particular. C57BL/6 mice received local heart irradiation with X-ray doses of 8 and 16 gray (Gy) at the age of 8 weeks. The mice were sacrificed 16 weeks later. Radiation-induced changes in the cardiac proteome were quantified using the Isotope Coded Protein Label (ICPL) method followed by mass spectrometry and software analysis. Significant alterations were observed in proteins involved in lipid metabolism and oxidative phosphorylation. Ionizing radiation markedly changed the phosphorylation and ubiquitination status of PPAR alpha. This was reflected as decreased expression of its target genes involved in energy metabolism and mitochondrial respiratory chain confirming the proteomics data. This study suggests that persistent alteration of cardiac metabolism due to impaired PPAR alpha activity contributes to the heart pathology after radiation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ionizing Radiation; Proteomics; ICPI; PPAR alpha; Endothelial Cell; Heart; Cardiovascular Disease; Activated Receptor-alpha ; Mitochondrial-transcription-factor ; Induced Genomic Instability ; Breast-cancer ; Myocardial-infarction ; Oxidative Stress ; Cardiovascular-disease ; Ionizing-radiation ; Cardiac Physiology ; Down-regulation
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Zeitschrift Journal of Proteome Research
Quellenangaben Band: 12, Heft: 6, Seiten: 2700-2714 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
Institute of Biological and Medical Imaging (IBMI)
POF Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Radiation Sciences
Enabling and Novel Technologies
PSP-Element(e) G-500200-001
G-505700-001
G-500300-001
G-500390-001
G-521400-001
PubMed ID 23560462
DOI 10.1021/pr400071g
WOS ID WOS:000320298600032
Scopus ID 84879354970
Erfassungsdatum 2013-05-03
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