100th Anniversary of Nobel Prize in Physiology or Medicine 1922: Metabolism in Muscle

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Metabolism".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 8934

Special Issue Editor


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Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
Interests: cancer cachexia; skeletal muscle; extacellular vesicles; regeneration; homeostasis; miofibers; mitochondrial biogenesis

Special Issue Information

Dear Colleagues,

The 1922 Nobel Prize in Physiology or Medicine was divided equally between Archibald Vivian Hill "for his discovery of heat generation in muscle" and Otto Fritz Meyerhof "for his discovery of the fixed relationship between oxygen consumption and lactic acid metabolism in muscle."

Both scientists’ research was concerned with muscle tissue.

Archibald Vivian Hill discovered that in order to work, our muscles need energy, which is released by chemical processes. He had been studying this process since the 1910s. He discovered that energy comes from a sequence of chemical processes, the first being independent of oxygen consumption and the second requiring oxygen.

Otto Fritz Meyerhof discovered that the conversions between carbohydrates and lactic acid play an important role in producing the energy that muscle needs to work. He demonstrated that lactic acid is produced from carbohydrates during muscle work and that lactic acid is burned and recycled from carbohydrates during recovery.

The discoveries of these two scientists, who were awarded the Nobel Prize in Medicine and Physiology, are a milestone in the study of skeletal muscle metabolism. A hundred years after their discovery, much more new information has been added to the ideas of these two scientists.

These 100 years have also seen the discovery of many similarities between skeletal muscle and cardiac muscle, the two striated muscle tissues of our body.

The new discoveries about satellite cells or progenitor cells of both cardiac muscle and skeletal muscle are certainly very important. New genetic or cellular therapies have been discovered to improve cardiac health or to improve the clinical condition of many patients with muscular dystrophy.

However, new discoveries are still needed because many muscle diseases, such as Duchenne dystrophy, still affect many people with no real cure, only palliative remedies.

This Special Issue aims to collect new discoveries that may lead to new advances in the field of muscle diseases in general, both skeletal and cardiac.

Dr. Valentina Di Felice
Guest Editor

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Keywords

  • exercise training
  • striated muscle
  • muscle regeneration
  • muscular dystrophy
  • muscle wasting
  • muscle metabolism

Published Papers (3 papers)

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Research

17 pages, 4283 KiB  
Article
Physiactisome: A New Nanovesicle Drug Containing Heat Shock Protein 60 for Treating Muscle Wasting and Cachexia
by Valentina Di Felice, Rosario Barone, Eleonora Trovato, Daniela D’Amico, Filippo Macaluso, Claudia Campanella, Antonella Marino Gammazza, Vera Muccilli, Vincenzo Cunsolo, Patrizia Cancemi, Gabriele Multhoff, Dario Coletti, Sergio Adamo, Felicia Farina and Francesco Cappello
Cells 2022, 11(9), 1406; https://doi.org/10.3390/cells11091406 - 21 Apr 2022
Cited by 4 | Viewed by 2382
Abstract
Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched [...] Read more.
Currently, no commercially available drugs have the ability to reverse cachexia or counteract muscle wasting and the loss of lean mass. Here, we report the methodology used to develop Physiactisome—a conditioned medium released by heat shock protein 60 (Hsp60)—overexpressing C2C12 cell lines enriched with small and large extracellular vesicles. We also present evidence supporting its use in the treatment of cachexia. Briefly, we obtain a nanovesicle-based secretion by genetically modifying C2C12 cell lines with an Hsp60-overexpressing plasmid. The secretion is used to treat naïve C2C12 cell lines. Physiactisome activates the expression of PGC-1α isoform 1, which is directly involved in mitochondrial biogenesis and muscle atrophy suppression, in naïve C2C12 cell lines. Proteomic analyses show Hsp60 localisation inside isolated nanovesicles and the localisation of several apocrine and merocrine molecules, with potential benefits for severe forms of muscle atrophy. Considering that Physiactisome can be easily obtained following tissue biopsy and can be applied to autologous muscle stem cells, we propose a potential nanovesicle-based anti-cachexia drug that could mimic the beneficial effects of exercise. Thus, Physiactisome may improve patient survival and quality of life. Furthermore, the method used to add Hsp60 into nanovesicles can be used to deliver other drugs or active proteins to vesicles. Full article
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16 pages, 5348 KiB  
Article
Fusion of Normoxic- and Hypoxic-Preconditioned Myoblasts Leads to Increased Hypertrophy
by Tamara Pircher, Henning Wackerhage, Elif Akova, Wolfgang Böcker, Attila Aszodi and Maximilian M. Saller
Cells 2022, 11(6), 1059; https://doi.org/10.3390/cells11061059 - 21 Mar 2022
Cited by 3 | Viewed by 2519
Abstract
Injuries, high altitude, and endurance exercise lead to hypoxic conditions in skeletal muscle and sometimes to hypoxia-induced local tissue damage. Thus, regenerative myoblasts/satellite cells are exposed to different levels and durations of partial oxygen pressure depending on the spatial distance from the blood [...] Read more.
Injuries, high altitude, and endurance exercise lead to hypoxic conditions in skeletal muscle and sometimes to hypoxia-induced local tissue damage. Thus, regenerative myoblasts/satellite cells are exposed to different levels and durations of partial oxygen pressure depending on the spatial distance from the blood vessels. To date, it is unclear how hypoxia affects myoblasts proliferation, differentiation, and particularly fusion with normoxic myoblasts. To study this, we investigated how 21% and 2% oxygen affects C2C12 myoblast morphology, proliferation, and myogenic differentiation and evaluated the fusion of normoxic- or hypoxic-preconditioned C2C12 cells in 21% or 2% oxygen in vitro. Out data show that the long-term hypoxic culture condition does not affect the proliferation of C2C12 cells but leads to rounder cells and reduced myotube formation when compared with myoblasts exposed to normoxia. However, when normoxic- and hypoxic-preconditioned myoblasts were differentiated together, the resultant myotubes were significantly larger than the control myotubes. Whole transcriptome sequencing analysis revealed several novel candidate genes that are differentially regulated during the differentiation under normoxia and hypoxia in mixed culture conditions and may thus be involved in the increase in myotube size. Taken together, oxygen-dependent adaption and interaction of myoblasts may represent a novel approach for the development of innovative therapeutic targets. Full article
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21 pages, 4644 KiB  
Article
Anabolic Factors and Myokines Improve Differentiation of Human Embryonic Stem Cell Derived Skeletal Muscle Cells
by Travis Ruan, Dylan Harney, Yen Chin Koay, Lipin Loo, Mark Larance and Leslie Caron
Cells 2022, 11(6), 963; https://doi.org/10.3390/cells11060963 - 11 Mar 2022
Cited by 1 | Viewed by 3027
Abstract
Skeletal muscle weakness is linked to many adverse health outcomes. Current research to identify new drugs has often been inconclusive due to lack of adequate cellular models. We previously developed a scalable monolayer system to differentiate human embryonic stem cells (hESCs) into mature [...] Read more.
Skeletal muscle weakness is linked to many adverse health outcomes. Current research to identify new drugs has often been inconclusive due to lack of adequate cellular models. We previously developed a scalable monolayer system to differentiate human embryonic stem cells (hESCs) into mature skeletal muscle cells (SkMCs) within 26 days without cell sorting or genetic manipulation. Here, building on our previous work, we show that differentiation and fusion of myotubes can be further enhanced using the anabolic factors testosterone (T) and follistatin (F) in combination with a cocktail of myokines (C). Importantly, combined TFC treatment significantly enhanced both the hESC-SkMC fusion index and the expression levels of various skeletal muscle markers, including the motor protein myosin heavy chain (MyHC). Transcriptomic and proteomic analysis revealed oxidative phosphorylation as the most up-regulated pathway, and a significantly higher level of ATP and increased mitochondrial mass were also observed in TFC-treated hESC-SkMCs, suggesting enhanced energy metabolism is coupled with improved muscle differentiation. This cellular model will be a powerful tool for studying in vitro myogenesis and for drug discovery pertaining to further enhancing muscle development or treating muscle diseases. Full article
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