1. Mitochondria can substitute for parvalbumin to lowercytosolic calcium levels in the murine fast skeletal muscleLorenzo Marcucci, Leonardo Nogara, Marta Canato, Elena Germinario, Anna Raffaello, Michela Carraro, Paolo Bernardi, Laura Pietrangelo, Simona Boncompagni, Feliciano Protasi, Nazareno Paolocci, Carlo Reggiani, 2024, izvirni znanstveni članek Povzetek: Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal musclefibers. Previous work showed that PV ablation has a limited impact on cytosolicCa2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochon-drial density and mitochondrial matrix-free calcium concentration ([Ca2+]mito).Here, we aimed to quantitatively test the hypothesis that mitochondria act tocompensate for PV deficiency.Methods: We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanicstimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a re-action–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptakeand storage capacity requirements to compensate for PV lack and analyzed pos-sible extracellular export.Results: [Ca 2+]mito during tetanic stimulation is greater in knock-out (KO)(1362 ± 392 nM) than in wild-type (WT) (855 ± 392 nM), p < 0.05. Under the as-sumption of a non-linear intramitochondrial buffering, the model predicts an ac-cumulation of 725 μmoles/Lfiber (buffering ratio 1:11 000) in KO, much higherthan in WT (137 μmoles/Lfiber, ratio 1:4500). The required transport rate via mi-tochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with availableliterature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store- operated calcium entry in KO compared to WT. However,levels of [Ca 2+]cyto during tetanic stimulation were not modulated to variations ofextracellular calcium.Conclusions: The model-based analysis of experimentally determined calciumdistribution during tetanic stimulation showed that mitochondria can act as abuffer to compensate for the lack of PV. This result contributes to a better under-standing of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers. Ključne besede: calcium, mitochondria, mouse skeletal muscle fibers, parvalbumin, reaction-diffusion model Objavljeno v DiRROS: 13.11.2024; Ogledov: 107; Prenosov: 67 Celotno besedilo (3,97 MB) Gradivo ima več datotek! Več... |
2. Spaceflight on the ISS changed the skeletal muscle proteome of two astronautsMarta Murgia, Joern Rittweger, Carlo Reggiani, Roberto Bottinelli, Matthias Mann, Stefano Schiaffino, Marco Vicenzo Narici, 2024, izvirni znanstveni članek Povzetek: Skeletal muscle undergoes atrophy and loss of force during long space missions, when astronauts are persistently exposed to altered gravity and increased ionizing radiation. We previously carried out mass spectrometry-based proteomics from skeletal muscle biopsies of two astronauts, taken before and after a mission on the International Space Station. The experiments were part of an effort to find similarities between spaceflight and bed rest, a ground-based model of unloading, focused on proteins located at the costameres. We here extend the data analysis of the astronaut dataset and show compartment-resolved changes in the mitochondrial proteome, remodeling of the extracellular matrix and of the antioxidant response. The astronauts differed in their level of onboard physical exercise, which correlated with their respective preservation of muscle mass and force at landing in previous analyses. We show that the mitochondrial proteome downregulation during spaceflight, particularly the inner membrane and matrix, was dramatic for both astronauts. The expression of autophagy regulators and reactive oxygen species scavengers, however, showed partially opposite expression trends in the two subjects, possibly correlating with their level of onboard exercise. As mitochondria are primarily affected in many different tissues during spaceflight, we hypothesize that reactive oxygen species (ROS) rather than mechanical unloading per se could be the primary cause of skeletal muscle mitochondrial damage in space. Onboard physical exercise might have a strong direct effect on the prevention of muscle atrophy through mechanotransduction and a subsidiary effect on mitochondrial quality control, possibly through upregulation of autophagy and anti-oxidant responses. Ključne besede: skeletal muscles, microgravity, muscle atrophy, autophagy Objavljeno v DiRROS: 12.11.2024; Ogledov: 120; Prenosov: 71 Celotno besedilo (1,55 MB) Gradivo ima več datotek! Več... |
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4. Infuence of age on force and re‑lengthening dynamics after tetanic stimulation withdrawal in the tibialis anterior muscleM. Cogliati, A. Cudicio, M. Benedini, H. V. Cabral, Francesco Negro, Carlo Reggiani, C. Orizio, 2023, izvirni znanstveni članek Ključne besede: aging, rate of torque reduction, relaxation process, stimulation Objavljeno v DiRROS: 18.12.2023; Ogledov: 630; Prenosov: 255 Celotno besedilo (1,64 MB) Gradivo ima več datotek! Več... |
5. Upregulation of sarcolemmal hemichannels and inflammatory transcripts with neuromuscular junction instability during lower limb unloading in humansGiuseppe Sirago, Julián Candia, Martino V. Franchi, Fabio Sarto, Elena Monti, Luana Toniolo, Carlo Reggiani, Emiliana Giacomello, Sandra Zampieri, Marco Vicenzo Narici, 2023, izvirni znanstveni članek Ključne besede: skeletal muscles, neuromuscular junction, sarcolemmal hemichannels, lower limb Objavljeno v DiRROS: 14.12.2023; Ogledov: 675; Prenosov: 280 Celotno besedilo (4,79 MB) Gradivo ima več datotek! Več... |
6. Sarcopenia parameters in active older adults – an eight-year longitudinal studyKaja Teraž, Uroš Marušič, Miloš Kalc, Boštjan Šimunič, Primož Pori, Bruno Grassi, Stefano Lazzer, Marco Vicenzo Narici, Mojca Gabrijelčič Blenkuš, Pietro Enrico Di Prampero, Carlo Reggiani, Angelina Passaro, Gianni Biolo, Mladen Gasparini, Rado Pišot, 2023, izvirni znanstveni članek Povzetek: Background Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. Methods The 52 active older adults (22 men and 30 women, mean age: 68.4±5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants’ overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. Results In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p<.001), muscle mass index (-5.4%; p<.001), and physical performance measured with gait speed (-28.6%; p<.001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p=.030 and −48.5%; p<.001, respectively). Conclusions Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. Trial registration The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531 Ključne besede: elderly, physical activities, sedentary behavior, skeletal muscle disorder, sarcopenia Objavljeno v DiRROS: 29.05.2023; Ogledov: 659; Prenosov: 354 Celotno besedilo (1,47 MB) Gradivo ima več datotek! Več... |
7. Irisin attenuates muscle impairment during bed rest through muscle-adipose tissue crosstalkAndrea D'Amuri, Juana Maria Sanz, Stefano Lazzer, Rado Pišot, Boštjan Šimunič, Gianni Biolo, Giovanni Zuliani, Mladen Gasparini, Marco Vicenzo Narici, Bruno Grassi, Carlo Reggiani, Edoardo Dalla Nora, Angelina Passaro, 2022, izvirni znanstveni članek Povzetek: Simple Summary: Irisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity.Abstract: The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR. Ključne besede: physical inactivity, bed rest, FNDC5 gene expression, myokines, sarcopenia, muscles fiber Objavljeno v DiRROS: 07.07.2022; Ogledov: 1180; Prenosov: 637 Celotno besedilo (798,63 KB) Gradivo ima več datotek! Več... |
8. Neuromuscular junction instability and altered intracellular calcium handling as early determinants of force loss during unloading in humansElena Monti, Carlo Reggiani, Martino V. Franchi, Luana Toniolo, Marco Sandri, Andrea Armani, Sandra Zampieri, Boštjan Šimunič, Rado Pišot, Marco Vicenzo Narici, 2021, izvirni znanstveni članek Povzetek: Unloading induces rapid skeletal muscle atrophy and functional decline. Importantly, force is lost at a much higher rate than muscle mass. We aimed to investigate the early determinants of the disproportionate loss of force compared to that of muscle mass in response to unloading. Ten young participants underwent 10 days of bed rest (BR). At baseline (BR0) and at 10 days (BR10), quadriceps femoris (QF) volume (VOL) and isometric maximum voluntary contraction (MVC) were assessed. At BR0 and BR10 blood samples and biopsies of vastus lateralis (VL) muscle were collected. Neuromuscular junction (NMJ) stability and myofibre innervation status were assessed, together with single fibre mechanical properties and sarcoplasmic reticulum (SR) calcium handling. From BR0 to BR10, QFVOL and MVC decreased by 5.2% (P = 0.003) and 14.3% (P < 0.001), respectively. Initial and partial denervation was detected from increased neural cell adhesion molecule (NCAM)-positive myofibres at BR10 compared with BR0 (+3.4%, P = 0.016). NMJ instability was further inferred from increased C-terminal agrin fragment concentration in serum (+19.2% at BR10, P = 0.031). Fast fibre cross-sectional area (CSA) showed a trend to decrease by 15% (P = 0.055) at BR10, while single fibre maximal tension (force/CSA) was unchanged. However, at BR10 SR Ca2+ release in response to caffeine decreased by 35.1% (P < 0.002) and 30.2% (P < 0.001) in fast and slow fibres, respectively, pointing to an impaired excitation%contraction coupling. These findings support the view that the early onset of NMJ instability and impairment in SR function are eligible mechanisms contributing to the greater decline in muscle force than in muscle size during unloading. Ključne besede: Ca2+ dynamics, muscle atrophy, neuromuscular junction instability, sarcoplasmic reticulum, single fibre atrophy, single fibre contractile impairment, unloading Objavljeno v DiRROS: 16.06.2021; Ogledov: 1574; Prenosov: 1364 Celotno besedilo (3,39 MB) Gradivo ima več datotek! Več... |