GeneLab Database Analyses Suggest Long-Term Impact of Space Radiation on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species

• Published in: International journal of molecular sciences 2019-02, Vol.20 (3), p.661
• Main Authors: Beheshti, Afshin, McDonald, J Tyson, Miller, Jack, Grabham, Peter, Costes, Sylvain V
• Format: Article
• Language: English
• Subjects: Aerospace environments; Atomic properties; BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology; Biology; Cardiomyocytes; cardiovascular; Cardiovascular disease; Cardiovascular diseases; Cardiovascular system; Chemistry; Coronary artery disease; Cosmic rays; Datasets; Disease control; DNA methylation; Endothelial cells; Experiments; Extraterrestrial radiation; Fission weapons; FYN; Fyn protein; GeneLab; Health risk assessment; Heart diseases; HUVECs; Hypertension; Hypoxia; HZE irradiation; Impact analysis; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Ionizing radiation; iron; Iron isotopes; Ischemia; Laboratories; Nervous system; protons; Radiation effects; reactive oxygen species; ROS; Space flight; space radiation; Space stations; Studies; Umbilical vein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20030661

Space radiation has recently been considered a risk factor for astronauts' cardiac health. As an example, for the case of how to query and identify datasets within NASA's GeneLab database and demonstrate the database utility, we used an unbiased systems biology method for identifying key genes/drivers for the contribution of space radiation on the cardiovascular system. This knowledge can contribute to designing appropriate experiments targeting these specific pathways. Microarray data from cardiomyocytes of male C57BL/6 mice followed-up for 28 days after exposure to 900 mGy of 1 GeV proton or 150 mGy of 1 GeV/n Fe were compared to human endothelial cells (HUVECs) cultured for 7 days on the International Space Station (ISS). We observed common molecular pathways between simulated space radiation and HUVECs flown on the ISS. The analysis suggests is the central driver/hub for the cardiovascular response to space radiation: the known oxidative stress induced immediately following radiation would only be transient and would upregulate , which in turn would reduce reactive oxygen species (ROS) levels, protecting the cardiovascular system. The transcriptomic signature of exposure to protons was also much closer to the spaceflight signature than Fe's signature. To our knowledge, this is the first time GeneLab datasets were utilized to provide potential biological indications that the majority of ions on the ISS are protons, clearly illustrating the power of omics analysis. More generally, this work also demonstrates how to combine animal radiation studies done on the ground and spaceflight studies to evaluate human risk in space.