Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human
Abstract Background Astronauts in Earth's orbit experience microgravity, resulting in a decline of skeletal muscle mass and function. On Earth, models simulating microgravity have shown that the extent of the loss in muscle force is greater than the loss in muscle mass. The reasons behind this...
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Wiley
2024-12-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13559 |
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| author | Mathias Velarde Michel‐Yves Sempore Valentine Allibert Valérie Montel Josiane Castells Loïc Treffel Angèle Chopard Thomas Brioche Laetitia Cochon Jérome Morel Bruno Bastide Anne‐Cécile Durieux Laurence Stevens Damien Freyssenet |
| author_facet | Mathias Velarde Michel‐Yves Sempore Valentine Allibert Valérie Montel Josiane Castells Loïc Treffel Angèle Chopard Thomas Brioche Laetitia Cochon Jérome Morel Bruno Bastide Anne‐Cécile Durieux Laurence Stevens Damien Freyssenet |
| author_sort | Mathias Velarde |
| collection | DOAJ |
| description | Abstract Background Astronauts in Earth's orbit experience microgravity, resulting in a decline of skeletal muscle mass and function. On Earth, models simulating microgravity have shown that the extent of the loss in muscle force is greater than the loss in muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. In the present study, we hypothesize that alongside the loss in skeletal muscle mass, modifications in the expression profile of genes encoding critical determinants of resting membrane potential, excitation‐contraction coupling and Ca2+ handling contribute to the decline in skeletal muscle force. Methods Healthy male volunteers (n = 18) participated in a 5‐day dry immersion (DI) study, an Earth‐based model of simulated microgravity. Muscle force measurement and MRI analysis of the cross‐sectional area of thigh muscles were performed before and after DI. Biopsies of the vastus lateralis skeletal muscle performed before and after DI were used for the determination Ca2+ properties of isolated muscle fibres, molecular and biochemical analyses. Results The extent of the decline in force, measured as maximal voluntary contraction of knee extensors (−11.1%, P < 0.01) was higher than the decline in muscle mass (−2.5%, P < 0.01). The decline in muscle mass was molecularly supported by a significant repression of the anabolic IGF‐1/Akt/mTOR pathway (−19.9% and −40.9% in 4E‐BP1 and RPS6 phosphorylation, respectively), a transcriptional downregulation of the autophagy‐lysosome pathway and a downregulation in the mRNA levels of myofibrillar protein slow isoforms. At the single fibre level, biochemical and tension‐pCa curve analyses showed that the loss in force was independent of fibre type (−11% and −12.3% in slow and fast fibres, respectively) and Ca2+ activation properties. Finally, we showed a significant remodelling in the expression of critical players of resting membrane potential (aquaporin 4: −24.9%, ATP1A2: +50.4%), excitation‐contraction coupling (CHRNA1: +75.1%, CACNA2D1: −23.5%, JPH2: −24.2%, TRDN: −15.6%, S100A1: +27.2%), and Ca2+ handling (ATP2A2: −32.5%, CASQ1: −15%, ORAI1: −36.2%, ATP2B1: −19.1%). Conclusions These findings provide evidence that a deregulation in the expression profile of critical molecular determinants of resting membrane potential, excitation‐contraction coupling, and Ca2+ handling could be involved in the loss of muscle force induced by DI. They also provide the paradigm for the understanding of muscle force loss during prolonged bed rest periods as those encountered in intensive care unit. |
| format | Article |
| id | doaj-art-af286edd1f284dc39fba1e28f22925c8 |
| institution | OA Journals |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-af286edd1f284dc39fba1e28f22925c82025-08-20T01:58:56ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092024-12-011562323233710.1002/jcsm.13559Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in humanMathias Velarde0Michel‐Yves Sempore1Valentine Allibert2Valérie Montel3Josiane Castells4Loïc Treffel5Angèle Chopard6Thomas Brioche7Laetitia Cochon8Jérome Morel9Bruno Bastide10Anne‐Cécile Durieux11Laurence Stevens12Damien Freyssenet13Laboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceUniv. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 ‐ URePSSS ‐ Unité de Recherche Pluridisciplinaire Sport Santé Société Lille FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceInstitut Toulousain d'Ostéopathie, IRF'O Toulouse FranceDMEM, INRAE Université Montpellier Montpellier FranceDMEM, INRAE Université Montpellier Montpellier FranceUniv. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 ‐ URePSSS ‐ Unité de Recherche Pluridisciplinaire Sport Santé Société Lille FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceUniv. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 ‐ URePSSS ‐ Unité de Recherche Pluridisciplinaire Sport Santé Société Lille FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceUniv. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 ‐ URePSSS ‐ Unité de Recherche Pluridisciplinaire Sport Santé Société Lille FranceLaboratoire Interuniversitaire de Biologie de la Motricité Université Jean Monnet‐Saint‐Etienne Saint Etienne FranceAbstract Background Astronauts in Earth's orbit experience microgravity, resulting in a decline of skeletal muscle mass and function. On Earth, models simulating microgravity have shown that the extent of the loss in muscle force is greater than the loss in muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. In the present study, we hypothesize that alongside the loss in skeletal muscle mass, modifications in the expression profile of genes encoding critical determinants of resting membrane potential, excitation‐contraction coupling and Ca2+ handling contribute to the decline in skeletal muscle force. Methods Healthy male volunteers (n = 18) participated in a 5‐day dry immersion (DI) study, an Earth‐based model of simulated microgravity. Muscle force measurement and MRI analysis of the cross‐sectional area of thigh muscles were performed before and after DI. Biopsies of the vastus lateralis skeletal muscle performed before and after DI were used for the determination Ca2+ properties of isolated muscle fibres, molecular and biochemical analyses. Results The extent of the decline in force, measured as maximal voluntary contraction of knee extensors (−11.1%, P < 0.01) was higher than the decline in muscle mass (−2.5%, P < 0.01). The decline in muscle mass was molecularly supported by a significant repression of the anabolic IGF‐1/Akt/mTOR pathway (−19.9% and −40.9% in 4E‐BP1 and RPS6 phosphorylation, respectively), a transcriptional downregulation of the autophagy‐lysosome pathway and a downregulation in the mRNA levels of myofibrillar protein slow isoforms. At the single fibre level, biochemical and tension‐pCa curve analyses showed that the loss in force was independent of fibre type (−11% and −12.3% in slow and fast fibres, respectively) and Ca2+ activation properties. Finally, we showed a significant remodelling in the expression of critical players of resting membrane potential (aquaporin 4: −24.9%, ATP1A2: +50.4%), excitation‐contraction coupling (CHRNA1: +75.1%, CACNA2D1: −23.5%, JPH2: −24.2%, TRDN: −15.6%, S100A1: +27.2%), and Ca2+ handling (ATP2A2: −32.5%, CASQ1: −15%, ORAI1: −36.2%, ATP2B1: −19.1%). Conclusions These findings provide evidence that a deregulation in the expression profile of critical molecular determinants of resting membrane potential, excitation‐contraction coupling, and Ca2+ handling could be involved in the loss of muscle force induced by DI. They also provide the paradigm for the understanding of muscle force loss during prolonged bed rest periods as those encountered in intensive care unit.https://doi.org/10.1002/jcsm.13559Excitation‐contraction couplingMicrogravityMuscle atrophyMuscle disuseSlow and fast isoforms of myofibrillar proteins |
| spellingShingle | Mathias Velarde Michel‐Yves Sempore Valentine Allibert Valérie Montel Josiane Castells Loïc Treffel Angèle Chopard Thomas Brioche Laetitia Cochon Jérome Morel Bruno Bastide Anne‐Cécile Durieux Laurence Stevens Damien Freyssenet Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human Journal of Cachexia, Sarcopenia and Muscle Excitation‐contraction coupling Microgravity Muscle atrophy Muscle disuse Slow and fast isoforms of myofibrillar proteins |
| title | Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| title_full | Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| title_fullStr | Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| title_full_unstemmed | Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| title_short | Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| title_sort | molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human |
| topic | Excitation‐contraction coupling Microgravity Muscle atrophy Muscle disuse Slow and fast isoforms of myofibrillar proteins |
| url | https://doi.org/10.1002/jcsm.13559 |
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