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Nat. Commun., Jun 11 2024, 15 (1) | https://doi.org/10.1038/s41467-024-48841-w Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight

Nadia Houerbi ^1,2,18, JangKeun Kim ^1,2,18, Eliah G. Overbey ^1,2, Richa Batra ¹, Annalise Schweickart ^2,3, Laura Patras^4,5, Serena Lucotti ^4,6, Krista A. Ryon ¹, Deena Najjar ¹, Cem Meydan ^1,2, Namita Damle ¹, Christopher Chin ^1,2, S. Anand Narayanan ⁷, Joseph W. Guarnieri ⁸, Gabrielle Widjaja ⁸, Afshin Beheshti^9,10, Gabriel Tobias ^4,11, Fanny Vatter ^4,11, Jeremy Wain Hirschberg¹, Ashley Kleinman ¹, Evan E. Afshin ^1,2, Matthew MacKay ^1,2, Qiuying Chen ⁶, Dawson Miller ⁶, Aaron S. Gajadhar ¹¹, Lucy Williamson¹¹, Purvi Tandel ¹¹, Qiu Yang¹¹, Jessica Chu ¹¹, Ryan Benz ¹¹, Asim Siddiqui ¹¹, Daniel Hornburg¹¹, Steven Gross ⁶, Bader Shirah ¹², Jan Krumsiek^2,3, Jaime Mateus ¹³, Xiao Mao ¹⁴, Irina Matei ^4,15,*& Christopher E. Mason ^{1,2,3,16,17,*}

¹Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
²The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
³Tri-Institutional Biology and Medicine program, Weill Cornell Medicine, New York, NY 10021, USA.
⁴Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY, USA.
⁵Department of Molecular Biology and Biotechnology, Center of Systems Biology, Biodiversity and Bioresources, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania.
⁶Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
⁷Department of Nutrition & Integrative Physiology, Florida State University, Tallahassee, FL, USA.
⁸Center of Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁹Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA.
¹¹Seer, Inc., Redwood City, CA 94065, USA.
¹²Department of Neuroscience, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia.
¹³Space Exploration Technologies Corporation (SpaceX), Hawthorne, CA, USA.
¹⁴Department of Basic Sciences, Division of Biomedical Engineering Sciences (BMES), Loma Linda University Health, Loma Linda, CA 92350, USA.
¹⁵Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
¹⁶The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA.
¹⁷WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY 10021, USA.
¹⁸These authors contributed equally: Nadia Houerbi, JangKeun Kim.

^*Corresponding authors: correspondence to Irina Matei or Christopher E. Mason

Abstract

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.

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형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-13)
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