Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused <i>Vastus lateralis</i> Muscle in Long-Term Bedrest (Toulouse Cocktail Study)
Dieter Blottner,
Daniele Capitanio,
Gabor Trautmann,
Sandra Furlan,
Guido Gambara,
Manuela Moriggi,
Katharina Block,
Pietro Barbacini,
Enrica Torretta,
Guillaume Py,
Angèle Chopard,
Imre Vida,
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
Daniele Capitanio
Department of Biomedical Sciences for Health, University of Milan, Via Luigi Mangiagalli 31, 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. Institute of Neuroscience, 35121 Padova, Italy
Guido Gambara
Center of Space Medicine Berlin, 10115 Berlin, Germany
Manuela Moriggi
Department of Biomedical Sciences for Health, University of Milan, Via Luigi Mangiagalli 31, 20133 Milan, Italy
Katharina Block
Center of Space Medicine Berlin, 10115 Berlin, Germany
Pietro Barbacini
Department of Biomedical Sciences for Health, University of Milan, Via Luigi Mangiagalli 31, 20133 Milan, Italy
UFR STAPS, INRAE, Université de Montpellier, UMR 866 Dynamique et Métabolisme, 34060 Montpellier, France
Angèle Chopard
UFR STAPS, INRAE, Université de Montpellier, UMR 866 Dynamique et Métabolisme, 34060 Montpellier, France
Imre Vida
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
Pompeo Volpe
Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy
Cecilia Gelfi
Department of Biomedical Sciences for Health, University of Milan, Via Luigi Mangiagalli 31, 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
Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the Toulouse Cocktail bedrest (BR) study were used to assess efficacy of an antioxidant cocktail (polyphenols, omega-3, vitamin E, and selenium) to counteract the increased redox homeostasis and enhance the antioxidant defense response by using label-free LC–MS/MS and NITRO-DIGE (nitrosated proteins), qPCR, and laser confocal microscopy. Label-free LC–MS/MS indicated that treatment prevented the redox homeostasis dysregulation and promoted structural remodeling (TPM3, MYH7, MYBPC, MYH1, MYL1, HRC, and LUM), increment of RyR1, myogenesis (CSRP3), and skeletal muscle development (MUSTN1, LMNA, AHNAK). These changes were absent in the Placebo group. Glycolysis, tricarboxylic acid cycle (TCA), oxidative phosphorylation, fatty acid beta-oxidation, and mitochondrial transmembrane transport were normalized in treated subjects. Proteins involved in protein folding were also normalized, whereas protein entailed in ion homeostasis decreased. NITRO-DIGE analysis showed significant protein nitrosylation changes for CAT, CA3, SDHA, and VDAC2 in Treatment vs. Placebo. Similarly, the nuclear factor erythroid 2-related factor 2 (Nrf-2) antioxidant response element (Nrf-2 ARE) signaling pathway showed an enhanced response in the Treatment group. Increased nitrosative redox homeostasis and decreased antioxidant defense response were found in post-BR control (Placebo, n = 10) vs. the antioxidant cocktail treated group (Treatment, n = 10). Taken together, increased nitrosative redox homeostasis and muscle deterioration during BR-driven physical inactivity were prevented, whereas decreased antioxidant nitrosative stress defense response was attenuated by Treatment suggesting positive effects of the nutritional intervention protocol in bedrest.
