Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Autor:	Kidane YH; Center for Pediatric Bone Biology and Translational Research, Scottish Rite for Children, Dallas, TX, United States., Lee FH; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Smith MF; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Wang C; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Mirza JB; Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States., Sharma S; Stanton College Preparatory School, Jacksonville, FL, United States., Lobo AA; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Dewan KC; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Chen J; Department of Surgery, Duke University Medical Center, Durham, NC, United States.; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan., Diaz TE; Eshelman School of Pharmacy, Chapel Hill, NC, United States., Pla MM; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Foster MW; Duke Proteomics and Metabolomics Core Facility, Duke University Medical Center, Durham, NC, United States., Bowles DE; Department of Surgery, Duke University Medical Center, Durham, NC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2024 Apr 18; Vol. 15, pp. 1248276. Date of Electronic Publication: 2024 Apr 18 (Print Publication: 2024).
DOI:	10.3389/fphys.2024.1248276
Abstrakt:	Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR 5-ion ) develop cardiovascular dysfunction by 12 months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8 months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p -value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p -value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR 5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR 5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Kidane, Lee, Smith, Wang, Mirza, Sharma, Lobo, Dewan, Chen, Diaz, Pla, Foster and Bowles.)
Databáze:	MEDLINE
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