1. Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused Vastus lateralis Muscle in Long-Term Bedrest (Toulouse Cocktail Study)
- Author
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Blottner, D., Capitanio, D., Trautmann, G., Furlan, S., Gambara, G., Moriggi, M., Block, K., Barbacini, P., Torretta, E., Py, G., Chopard, A., Vida, I., Volpe, P., Gelfi, C., Salanova, M., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Milan, Institute of Neuroscience [Milan, Italy] (CNR), Center for Space Medicine Berlin, Università degli Studi di Milano, IRCCS Policlinico San Donato, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital of Padua, Federal Department of Economy and Energy (BMWi) through Deutsches Zentrum fuer Luft-und Raumfahrt (DLR e.V., Bonn-Oberkassel, Germany) 50WB1421/1718, 50WB1826, Agenzia Spaziale Italiana (ASI) 2018-9-U.O STOPBROS, and Charite-Universitatsmedizin Berlin
- Subjects
sarcopenia ,Antioxidant systems ,Bedrest muscle disuse ,Oxidative stress ,RNS in cell signaling ,Sarcopenia ,Skeletal muscle redox homeostasis ,lcsh:Therapeutics. Pharmacology ,skeletal muscle redox homeostasis ,lcsh:RM1-950 ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,oxidative stress ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,antioxidant systems ,bedrest muscle disuse ,Article - Abstract
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.
- Published
- 2021
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