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1دورية أكاديمية
المؤلفون: Britt Schoenrock, Paul E. Muckelt, Maria Hastermann, Kirsten Albracht, Robert MacGregor, David Martin, Hans-Christian Gunga, Michele Salanova, Maria J. Stokes, Martin B. Warner, Dieter Blottner
المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-13 (2024)
الوصف: Abstract Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate inflight assessment to inform exercise programmes is critical due to lack of technologies suitable for spaceflight. Changes in mechanical properties indicate muscle health status and can be measured rapidly and non-invasively using novel technology. A hand-held MyotonPRO device enabled monitoring of muscle health for the first time in spaceflight (> 180 days). Greater/maintained stiffness indicated countermeasures were effective. Tissue stiffness was preserved in the majority of muscles (neck, shoulder, back, thigh) but Tibialis Anterior (foot lever muscle) stiffness decreased inflight vs. preflight (p
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2045-2322
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2دورية أكاديمية
المؤلفون: 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
المصدر: Antioxidants, Vol 13, Iss 4, p 432 (2024)
مصطلحات موضوعية: spaceflight, nitric oxide synthase, microgravity, RONS, nitrosated proteins, Therapeutics. Pharmacology, RM1-950
الوصف: 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.
وصف الملف: electronic resource
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3دورية أكاديميةSkeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent
المؤلفون: Deeksha Malhan, Müge Yalçin, Britt Schoenrock, Dieter Blottner, Angela Relógio
المصدر: npj Microgravity, Vol 9, Iss 1, Pp 1-20 (2023)
مصطلحات موضوعية: Biotechnology, TP248.13-248.65, Physiology, QP1-981
الوصف: Abstract The circadian clock regulates cellular and molecular processes in mammals across all tissues including skeletal muscle, one of the largest organs in the human body. Dysregulated circadian rhythms are characteristic of aging and crewed spaceflight, associated with, for example, musculoskeletal atrophy. Molecular insights into spaceflight-related alterations of circadian regulation in skeletal muscle are still missing. Here, we investigated potential functional consequences of clock disruptions on skeletal muscle using published omics datasets obtained from spaceflights and other clock-altering, external (fasting and exercise), or internal (aging) conditions on Earth. Our analysis identified alterations of the clock network and skeletal muscle-associated pathways, as a result of spaceflight duration in mice, which resembles aging-related gene expression changes observed in humans on Earth (e.g., ATF4 downregulation, associated with muscle atrophy). Furthermore, according to our results, external factors such as exercise or fasting lead to molecular changes in the core-clock network, which may compensate for the circadian disruption observed during spaceflights. Thus, maintaining circadian functioning is crucial to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2373-8065
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4دورية أكاديمية
المؤلفون: Paul E. Muckelt, Martin B. Warner, Tom Cheliotis-James, Rachel Muckelt, Maria Hastermann, Britt Schoenrock, David Martin, Robert MacGregor, Dieter Blottner, Maria Stokes
المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)
الوصف: Abstract The assessment of muscle health is of paramount importance, as the loss of muscle mass and strength can affect performance. Two non-invasive tools that have been found to be useful in this are the MyotonPRO and rehabilitative ultrasound imaging, both have shown to be reliable in previous studies many of which conducted by the research team. This study aims to determine the reliability of previously unassessed local body structures and to determine their minimal detectable changes (MDC) to support both researchers and clinicians. Twenty healthy participants were recruited to determine the reliability of seven skin positions out of a previously established protocol. Reliability was determined between three independent raters, and day to day reliability was assessed with one rater a week apart. Intraclass Correlation Coefficients (ICC) between raters and between days for tissue stiffness, tone and elasticity range from moderate to excellent (ICC 0.52–0.97), with most good or excellent. ICCs for subcutaneous thickness between days was good or excellent (ICC 0.86–0.91) and moderate to excellent between raters (ICC 0.72–0.96), in muscles it was moderate to excellent between raters and days (ICC 0.71–0.95). The protocol in this study is repeatable with overall good reliability, it also provides established MDC values for several measurement points.
وصف الملف: electronic resource
Relation: https://doaj.org/toc/2045-2322
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5دورية أكاديمية
المؤلفون: Dieter Blottner, Manuela Moriggi, Gabor Trautmann, Maria Hastermann, Daniele Capitanio, Enrica Torretta, Katharina Block, Joern Rittweger, Ulrich Limper, Cecilia Gelfi, Michele Salanova
المصدر: International Journal of Molecular Sciences, Vol 24, Iss 4, p 4095 (2023)
مصطلحات موضوعية: skeletal muscle, proteomics, spaceflight, structural proteins, protein signaling pathways, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration.
وصف الملف: electronic resource
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6دورية أكاديمية
المؤلفون: Martin Schubert, Andreas Pelz, Gabor Trautmann, Katharina Block, Sandra Furlan, Martina Gutsmann, Siegfried Kohler, Pompeo Volpe, Dieter Blottner, Andreas Meisel, Michele Salanova
المصدر: International Journal of Molecular Sciences, Vol 23, Iss 23, p 15052 (2022)
مصطلحات موضوعية: skeletal muscle, Homer isoform expression, NMJ adaptation, Myasthenia Gravis, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity. Soleus (SOL), extensor digitorum longus (EDL) and gastrocnemius (GAS) skeletal muscles are investigated. nAChR membrane clusters were studied to monitor neuromuscular junction (NMJ) integrity. Fibre-type cross-sectional area (CSA) analysis is carried out in order to determine the extent of muscle atrophy. Our findings clearly showed that crosslinking activity of Homer long forms (Homer 1b/c and Homer2a/b) are decreased in slow-twitch and increased in fast-twitch muscle of EAMG whereas the short form of Homer that disrupts Homer crosslinking (Homer1a) is upregulated in slow-twitch muscle only. Densitometry analysis showed a 125% increase in Homer protein expression in EDL, and a 45% decrease in SOL of EAMG mice. In contrast, nAChR fluorescence pixel intensity decreased in endplates of EAMG mice, more distinct in type-I dominant SOL muscle. Morphometric CSA of EAMG vs. control (CTR) revealed a significant reduction in EDL but not in GAS and SOL. Taken together, these results indicate that postsynaptic Homer signalling is impaired in slow-twitch SOL muscle from EAMG mice and provide compelling evidence suggesting a functional coupling between Homer and nAChR, underscoring the key role of Homer in skeletal muscle neurophysiology.
وصف الملف: electronic resource
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7دورية أكاديمية
المؤلفون: Pietro Barbacini, Dieter Blottner, Daniele Capitanio, Gabor Trautmann, Katharina Block, Enrica Torretta, Manuela Moriggi, Michele Salanova, Cecilia Gelfi
المصدر: Cells, Vol 11, Iss 13, p 2120 (2022)
مصطلحات موضوعية: bed rest, S-nitrosylation, RONS, antioxidant, omega-3, serum apolipoproteins, Cytology, QH573-671
الوصف: Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study). The serum proteome, sphingolipidome and nitrosoproteome were analyzed adopting different mass spectrometry-based approaches. Results in placebo-treated BR subjects indicated a marked decrease of proteins associated with high-density lipoproteins (HDL) involved in lipemic homeostasis not found in the cocktail-treated BR group. Moreover, long-chain ceramides decreased while sphingomyelin increased in the BR cocktail-treated group. In placebo, the ratio of S-nitrosylated/total protein increased for apolipoprotein D and several proteins were over-nitrosylated. In cocktail-treated BR subjects, the majority of protein showed a pattern of under-nitrosylation, except for ceruloplasmin and hemopexin, which were over-nitrosylated. Collectively, data indicate a positive effect of the cocktail in preserving lipemic and RONS homeostasis in extended disuse conditions.
وصف الملف: electronic resource
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8دورية أكاديمية
المؤلفون: Alireza Basti, Müge Yalçin, David Herms, Janina Hesse, Ouda Aboumanify, Yin Li, Zita Aretz, Josefin Garmshausen, Rukeia El-Athman, Maria Hastermann, Dieter Blottner, Angela Relógio
المصدر: BMJ Open Sport & Exercise Medicine, Vol 7, Iss 1 (2021)
مصطلحات موضوعية: Medicine (General), R5-920
الوصف: Objectives In this study, we investigated daily fluctuations in molecular (gene expression) and physiological (biomechanical muscle properties) features in human peripheral cells and their correlation with exercise performance.Methods 21 healthy participants (13 men and 8 women) took part in three test series: for the molecular analysis, 15 participants provided hair, blood or saliva time-course sampling for the rhythmicity analysis of core-clock gene expression via RT-PCR. For the exercise tests, 16 participants conducted strength and endurance exercises at different times of the day (9h, 12h, 15h and 18h). Myotonometry was carried out using a digital palpation device (MyotonPRO), five muscles were measured in 11 participants. A computational analysis was performed to relate core-clock gene expression, resting muscle tone and exercise performance.Results Core-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15–18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance.Conclusion Training programmes can profit from these findings to increase efficiency and fine-tune timing of training sessions based on the individual molecular data. Our results can benefit both professional athletes, where a fraction of seconds may allow for a gold medal, and rehabilitation in clinical settings to increase therapy efficacy and reduce recovery times.
وصف الملف: electronic resource
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9دورية أكاديمية
المؤلفون: Dieter Blottner, Gabor Trautmann, Sandra Furlan, Guido Gambara, Katharina Block, Martina Gutsmann, Lian-Wen Sun, Paul F. Worley, Luisa Gorza, Martina Scano, Paola Lorenzon, Imre Vida, Pompeo Volpe, Michele Salanova
المصدر: International Journal of Molecular Sciences, Vol 23, Iss 1, p 75 (2021)
مصطلحات موضوعية: Homer isoform switch, NMJ adaptation, microgravity, hindlimb unloading, muscle atrophy, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (n = 5) housed for 30 days in space (Bion-flight = BF) compared to muscles from Bion biosatellite on the ground-housed animals (Bion ground = BG) and from standard cage housed animals (Flight control = FC). A comparison study was carried out with muscles of rats subjected to hindlimb unloading (HU). Gene array and qPCR results showed an increase in Homer1a transcripts, the short dominant negative isoform, in soleus (SOL) muscle after 30 days in microgravity, whereas it was only transiently increased after four days of HU. Conversely, Homer2 long-form was downregulated in SOL muscle in both models. Homer immunofluorescence intensity analysis at the NMJ of BF and HU animals showed comparable outcomes in SOL but not in the extensor digitorum longus (EDL) muscle. Reduced Homer crosslinking at the NMJ consequent to increased Homer1a and/or reduced Homer2 may contribute to muscle-type specific atrophy resulting from microgravity and HU disuse suggesting mutual mechanisms.
وصف الملف: electronic resource
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10دورية أكاديمية
المؤلفون: Coralie Arc-Chagnaud, Guillaume Py, Théo Fovet, Rémi Roumanille, Rémi Demangel, Allan F. Pagano, Pierre Delobel, Stéphane Blanc, Bernard J. Jasmin, Dieter Blottner, Michele Salanova, Mari-Carmen Gomez-Cabrera, José Viña, Thomas Brioche, Angèle Chopard
المصدر: Frontiers in Physiology, Vol 11 (2020)
مصطلحات موضوعية: muscle wasting, inactivity, oxidative stress, antioxidants, cell signaling, Physiology, QP1-981
الوصف: Understanding the molecular pathways involved in the loss of skeletal muscle mass and function induced by muscle disuse is a crucial issue in the context of spaceflight as well as in the clinical field, and development of efficient countermeasures is needed. Recent studies have reported the importance of redox balance dysregulation as a major mechanism leading to muscle wasting. Our study aimed to evaluate the effects of an antioxidant/anti-inflammatory cocktail (741 mg of polyphenols, 138 mg of vitamin E, 80 μg of selenium, and 2.1 g of omega-3) in the prevention of muscle deconditioning induced by long-term inactivity. The study consisted of 60 days of hypoactivity using the head-down bed rest (HDBR) model. Twenty healthy men were recruited; half of them received a daily antioxidant/anti-inflammatory supplementation, whereas the other half received a placebo. Muscle biopsies were collected from the vastus lateralis muscles before and after bedrest and 10 days after remobilization. After 2 months of HDBR, all subjects presented muscle deconditioning characterized by a loss of muscle strength and an atrophy of muscle fibers, which was not prevented by cocktail supplementation. Our results regarding muscle oxidative damage, mitochondrial content, and protein balance actors refuted the potential protection of the cocktail during long-term inactivity and showed a disturbance of essential signaling pathways (protein balance and mitochondriogenesis) during the remobilization period. This study demonstrated the ineffectiveness of our cocktail supplementation and underlines the complexity of redox balance mechanisms. It raises interrogations regarding the appropriate nutritional intervention to fight against muscle deconditioning.
وصف الملف: electronic resource
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