The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure
A central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and defects in this process profoundly affect the subsequent process of regeneration. High levels of react...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/10986 |
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| author | Roberta Ceci Guglielmo Duranti Stefano Giuliani Marianna Nicoletta Rossi Ivan Dimauro Stefania Sabatini Paolo Mariottini Manuela Cervelli |
| author_facet | Roberta Ceci Guglielmo Duranti Stefano Giuliani Marianna Nicoletta Rossi Ivan Dimauro Stefania Sabatini Paolo Mariottini Manuela Cervelli |
| author_sort | Roberta Ceci |
| collection | DOAJ |
| description | A central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and defects in this process profoundly affect the subsequent process of regeneration. High levels of reactive oxygen species such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) with the consequent formation of oxidized macromolecules increase myoblasts’ cell death and strongly contribute to the loss of myoblast function. Recently, particular interest has turned towards the beneficial effects on muscle of the naturally occurring polyamine spermidine (Spd). In this work, we tested the hypothesis that Spd, upon oxidative challenge, would restore the compromised myoblasts’ viability and redox status. The effects of Spd in combination with aminoguanidine (Spd-AG), an inhibitor of bovine serum amine oxidase, on murine C2C12 myoblasts treated with a mild dose of H<sub>2</sub>O<sub>2</sub> were evaluated by analyzing: (i) myoblast viability and recovery from wound scratch; (ii) redox status and (iii) polyamine (PAs) metabolism. The treatment of C2C12 myoblasts with Spd-AG increased cell number and accelerated scratch wound closure, while H<sub>2</sub>O<sub>2</sub> exposure caused redox status imbalance and cell death. The combined treatment with Spd-AG showed an antioxidant effect on C2C12 myoblasts, partially restoring cellular total antioxidant capacity, reducing the oxidized glutathione (GSH/GSSG) ratio and increasing cell viability through a reduction in cell death. Moreover, Spd-AG administration counteracted the induction of polyamine catabolic genes and PA content decreased due to H<sub>2</sub>O<sub>2</sub> challenges. In conclusion, our data suggest that Spd treatment has a protective role in skeletal muscle cells by restoring redox balance and promoting recovery from wound scratches, thus making myoblasts able to better cope with an oxidative insult. |
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| issn | 1661-6596 1422-0067 |
| language | English |
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| spelling | doaj.art-1a55f6d729244c8db353b95194a7e2782023-11-23T20:25:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191098610.3390/ijms231910986The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> ExposureRoberta Ceci0Guglielmo Duranti1Stefano Giuliani2Marianna Nicoletta Rossi3Ivan Dimauro4Stefania Sabatini5Paolo Mariottini6Manuela Cervelli7Laboratory of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, Università degli Studi di Roma “Foro Italico”, 00135 Rome, ItalyLaboratory of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, Università degli Studi di Roma “Foro Italico”, 00135 Rome, ItalyDepartment of Science, “Department of Excellence 2018–2022”, University of Rome “Roma Tre”, 00146 Rome, ItalyDepartment of Science, “Department of Excellence 2018–2022”, University of Rome “Roma Tre”, 00146 Rome, ItalyLaboratory of Biology and Genetics, Department of Movement, Human and Health Sciences, Università degli Studi di Roma “Foro Italico”, 00135 Rome, ItalyLaboratory of Biochemistry and Molecular Biology, Department of Movement, Human and Health Sciences, Università degli Studi di Roma “Foro Italico”, 00135 Rome, ItalyDepartment of Science, “Department of Excellence 2018–2022”, University of Rome “Roma Tre”, 00146 Rome, ItalyDepartment of Science, “Department of Excellence 2018–2022”, University of Rome “Roma Tre”, 00146 Rome, ItalyA central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and defects in this process profoundly affect the subsequent process of regeneration. High levels of reactive oxygen species such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) with the consequent formation of oxidized macromolecules increase myoblasts’ cell death and strongly contribute to the loss of myoblast function. Recently, particular interest has turned towards the beneficial effects on muscle of the naturally occurring polyamine spermidine (Spd). In this work, we tested the hypothesis that Spd, upon oxidative challenge, would restore the compromised myoblasts’ viability and redox status. The effects of Spd in combination with aminoguanidine (Spd-AG), an inhibitor of bovine serum amine oxidase, on murine C2C12 myoblasts treated with a mild dose of H<sub>2</sub>O<sub>2</sub> were evaluated by analyzing: (i) myoblast viability and recovery from wound scratch; (ii) redox status and (iii) polyamine (PAs) metabolism. The treatment of C2C12 myoblasts with Spd-AG increased cell number and accelerated scratch wound closure, while H<sub>2</sub>O<sub>2</sub> exposure caused redox status imbalance and cell death. The combined treatment with Spd-AG showed an antioxidant effect on C2C12 myoblasts, partially restoring cellular total antioxidant capacity, reducing the oxidized glutathione (GSH/GSSG) ratio and increasing cell viability through a reduction in cell death. Moreover, Spd-AG administration counteracted the induction of polyamine catabolic genes and PA content decreased due to H<sub>2</sub>O<sub>2</sub> challenges. In conclusion, our data suggest that Spd treatment has a protective role in skeletal muscle cells by restoring redox balance and promoting recovery from wound scratches, thus making myoblasts able to better cope with an oxidative insult.https://www.mdpi.com/1422-0067/23/19/10986spermidinepolyamines homeostasisglutathioneredox homeostasismyoblasts proliferation |
| spellingShingle | Roberta Ceci Guglielmo Duranti Stefano Giuliani Marianna Nicoletta Rossi Ivan Dimauro Stefania Sabatini Paolo Mariottini Manuela Cervelli The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure International Journal of Molecular Sciences spermidine polyamines homeostasis glutathione redox homeostasis myoblasts proliferation |
| title | The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure |
| title_full | The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure |
| title_fullStr | The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure |
| title_full_unstemmed | The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure |
| title_short | The Impact of Spermidine on C2C12 Myoblasts Proliferation, Redox Status and Polyamines Metabolism under H<sub>2</sub>O<sub>2</sub> Exposure |
| title_sort | impact of spermidine on c2c12 myoblasts proliferation redox status and polyamines metabolism under h sub 2 sub o sub 2 sub exposure |
| topic | spermidine polyamines homeostasis glutathione redox homeostasis myoblasts proliferation |
| url | https://www.mdpi.com/1422-0067/23/19/10986 |
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