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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways.
Int. J. Radiat. Biol. 93, 920-928 (2017)
PURPOSE: Epidemiological studies indicate that radiation doses as low as 0.5 Gy increase the risk of cardiovascular disease decades after the exposure. The aim of the present study was to investigate whether this radiation dose causes late molecular alterations in endothelial cells that could support the population-based data. MATERIALS AND METHODS: Human coronary artery endothelial cells were irradiated at 0.5 Gy (X-ray) and radiation-induced changes in the proteome were investigated after different time intervals (1, 7 and 14 d) using ICPL technology. Key changes identified by proteomics and bioinformatics were validated by immunoblotting and ELISA. RESULTS: The radiation-induced alteration of the endothelial proteome was characterized by sustained perturbation of Rho GDP-dissociation inhibitor (RhoGDI) and nitric oxide (NO) signalling pathways. At later time-points, this was accompanied by reduced proteasome activity, enhanced protein carbonylation indicating augmented oxidative stress, and senescence. CONCLUSIONS: These molecular changes are indicative of long-term premature endothelial dysfunction and provide a mechanistic framework to the epidemiological data showing increased risk of cardiovascular disease at 0.5 Gy.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Proteomics ; Cardiovascular Disease ; Endothelial Senescence ; Ionizing Radiation ; Proteasome; Nitric-oxide Synthase; Cardiovascular-diseases; Ionizing-radiation; Insulin-resistance; Dysfunction; Mechanisms; Gtpase; Tissue; Phosphorylation; Ubiquitination
ISSN (print) / ISBN
0955-3002
e-ISSN
1362-3095
Zeitschrift
International Journal of Radiation Biology
Quellenangaben
Band: 93,
Heft: 9,
Seiten: 920-928
Verlag
Informa Healthcare
Verlagsort
Abingdon
Begutachtungsstatus
Peer reviewed