The MYO experiment in the Foton-M 3 space flight mission

Loss of skeletal muscle mass and force occurs in si tuations of altered use such as denervation, immobilization, aging and microgravity . The atrophy program induced under these conditions leads to an enhanced muscle protei n degradation mainly via the ubiquitinproteasome and the autophagy-lysosome systems. The aim of our work is the definition of signaling pathways involved in muscle atrophy durin g space flights, that were never explored so far. As cellular model, we used culture d single skeletal muscle fibers isolated from adult mice. On September 2007, we had the uniq ue opportunity to expose skeletal muscle fibers to microgravity condition during the unmanned Russian Foton-M3 mission, sponsored by Italian Space Agency (ASI) LIFE progra m. We utilized six pre-existing STROMA bioreactors (produced by Kayser Italia), fou r of which were for molecular analyses and two for morphology. Here we report the results of this space flight experience whose specific objective was to determine the effec ts of launch mechanical solicitations and four days space flight on single muscle fibers. Electron microscopy and gene expression analyses showed that space flight caused only minor modifications to cultured muscle fibers. Importantly, Foton-M3 mission provid ed useful indications on the requirements necessary to develop a novel bioreacto r to be used in microgravity environment as well as in on ground experiments.

[1]  A. Goldberg,et al.  FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. , 2007, Cell metabolism.

[2]  A. Goldberg,et al.  FoxO3 controls autophagy in skeletal muscle in vivo. , 2007, Cell metabolism.

[3]  S. Clément,et al.  Dissociated flexor digitorum brevis myofiber culture system--a more mature muscle culture system. , 2007, Cell motility and the cytoskeleton.

[4]  A. Bigard,et al.  Quantification by real-time PCR of developmental and adult myosin mRNA in rat muscles. , 2006, Biochemical and biophysical research communications.

[5]  Marco Sandri,et al.  Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy , 2004, Cell.

[6]  I. Nonaka,et al.  Skeletal muscle gene expression in space‐flown rats , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  C. Putman,et al.  Effects of spaceflight on myosin heavy-chain content, fibre morphology and succinate dehydrogenase activity in rat diaphragm , 2004, Pflügers Archiv.

[8]  A. Goldberg,et al.  Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  B. Harrison,et al.  Skeletal muscle adaptations to microgravity exposure in the mouse. , 2003, Journal of applied physiology.

[10]  S. Bhasin,et al.  Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight. , 2002, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[11]  E. Calabria,et al.  A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[12]  F. Speleman,et al.  Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes , 2002, Genome Biology.

[13]  G. Yancopoulos,et al.  Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo , 2001, Nature Cell Biology.

[14]  R. Fitts,et al.  Functional and structural adaptations of skeletal muscle to microgravity. , 2001, The Journal of experimental biology.

[15]  I. Nonaka,et al.  Space shuttle flight (STS‐90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin‐proteasome pathway , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  S. Gordon,et al.  The effects of 10 days of spaceflight on the shuttle Endeavour on predominantly fast-twitch muscles in the rat , 2000, Histochemistry and Cell Biology.

[17]  H. Vandenburgh,et al.  Space travel directly induces skeletal muscle atrophy , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  N. Elvassore,et al.  Cultured adult muscle fibers in the microgravity environment. The MYO experiment in the Foton-M3 space flight mission , 2009 .

[19]  V R Edgerton,et al.  Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number. , 2002, Advances in space research : the official journal of the Committee on Space Research.

[20]  V. Edgerton,et al.  Fiber size and myosin phenotypes of selected Rhesus hindlimb muscles after a 14-day spaceflight. , 1999, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[21]  M Falempin,et al.  Muscle atrophy associated with microgravity in rat: basic data for countermeasures. , 1998, Acta astronautica.

[22]  D. Riley Review of primary spaceflight-induced and secondary reloading-induced changes in slow antigravity muscles of rats. , 1998, Advances in space research : the official journal of the Committee on Space Research.