Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways

Omid Azimzadeh, Vikram Subramanian, Susanne Ständer, Juliane Merl-Pham, Donna Lowe, Zarko Barjaktarovic, Simone Moertl, Ken Raj, Michael J. Atkinson, Soile Tapio

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)920-928
Number of pages9
JournalInternational Journal of Radiation Biology
Volume93
Issue number9
DOIs
Publication statusPublished - 2 Sep 2017

Keywords

  • cardiovascular disease
  • endothelial senescence
  • ionizing radiation
  • proteasome
  • Proteomics

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