Nitrosative Stress in Astronaut Skeletal Muscle in Spaceflight
Dieter Blottner,
Manuela Moriggi,
Gabor Trautmann,
Sandra Furlan,
Katharina Block,
Martina Gutsmann,
Enrica Torretta,
Pietro Barbacini,
Daniele Capitanio,
Joern Rittweger,
Ulrich Limper,
Pompeo Volpe,
Cecilia Gelfi,
Michele Salanova
Affiliations
Dieter Blottner
Institute of Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
Manuela Moriggi
Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
Gabor Trautmann
Institute of Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
Sandra Furlan
C.N.R. Neuroscience Institute, I-35121 Padova, Italy
Katharina Block
Institute of Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
Martina Gutsmann
Institute of Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
Enrica Torretta
Laboratory of Proteomics and Lipidomics, IRCCS Orthopedic Institute Galeazzi, Via R. Galeazzi 4, 20161 Milan, Italy
Pietro Barbacini
Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
Daniele Capitanio
Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
Joern Rittweger
Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany
Ulrich Limper
Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany
Pompeo Volpe
Department of Biomedical Sciences, Università di Padova, I-35121 Padova, Italy
Cecilia Gelfi
Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy
Michele Salanova
Institute of Integrative Neuroanatomy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany
Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR changes in deep calf soleus muscle. Nitro-DIGE analyses identified functional proteins (structural, metabolic, mitochondrial) that were over-nitrosylated post- vs. preflight. In a short-duration mission (SDM) astronaut (9 ISS days), s-nitrosylation of a nodal protein of the glycolytic flux, specific proteins in tricarboxylic acid (TCA) cycle, respiratory chain, and over-nitrosylation of creatine kinase M-types as signs of impaired ATP production and muscle contraction proteins were seen. S-nitrosylation of serotransferrin (TF) or carbonic anhydrase 3 (CA3b and 3c) represented signs of acute response microgravity muscle maladaptation. LDM nitrosoprofiles reflected recovery of mitochondrial activity, contraction proteins, and iron transporter TF as signs of muscle adaptation to microgravity. Nitrosated antioxidant proteins, alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR), and selenoprotein thioredoxin reductase 1 (TXNRD1) levels indicated signs of altered redox homeostasis and reduced protection from nitrosative stress in spaceflight. This work presents a novel spaceflight-generated dataset on s-nitrosylated muscle protein signatures from astronauts that helps both to better understand the structural and molecular networks associated to muscular nitrosative stress and to design countermeasures to dysfunction and impaired performance control in human spaceflight missions.
