Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels

The vegetal polyphenol curcumin displays beneficial effects against skeletal muscle derangement induced by oxidative stress, disuse or aging. Since oxidative stress and inflammation are involved in the progression of muscle dystrophy, the effects of curcumin administration were investigated in the d...

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Main Authors: Luisa Gorza, Elena Germinario, Maurizio Vitadello, Irene Guerra, Federica De Majo, Francesca Gasparella, Paolo Caliceti, Libero Vitiello, Daniela Danieli-Betto
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/12/6/1181
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author Luisa Gorza
Elena Germinario
Maurizio Vitadello
Irene Guerra
Federica De Majo
Francesca Gasparella
Paolo Caliceti
Libero Vitiello
Daniela Danieli-Betto
author_facet Luisa Gorza
Elena Germinario
Maurizio Vitadello
Irene Guerra
Federica De Majo
Francesca Gasparella
Paolo Caliceti
Libero Vitiello
Daniela Danieli-Betto
author_sort Luisa Gorza
collection DOAJ
description The vegetal polyphenol curcumin displays beneficial effects against skeletal muscle derangement induced by oxidative stress, disuse or aging. Since oxidative stress and inflammation are involved in the progression of muscle dystrophy, the effects of curcumin administration were investigated in the diaphragm of <i>mdx</i> mice injected intraperitoneally or subcutaneously with curcumin for 4–12–24 weeks. Curcumin treatment independently of the way and duration of administration (i) ameliorated myofiber maturation index without affecting myofiber necrosis, inflammation and degree of fibrosis; (ii) counteracted the decrease in type 2X and 2B fiber percentage; (iii) increased about 30% both twitch and tetanic tensions of diaphragm strips; (iv) reduced myosin nitrotyrosination and tropomyosin oxidation; (v) acted on two opposite nNOS regulators by decreasing active AMP-Kinase and increasing SERCA1 protein levels, the latter effect being detectable also in myotube cultures from <i>mdx</i> satellite cells. Interestingly, increased contractility, decreased myosin nitrotyrosination and SERCA1 upregulation were also detectable in the <i>mdx</i> diaphragm after a 4-week administration of the NOS inhibitor 7-Nitroindazole, and were not improved further by a combined treatment. In conclusion, curcumin has beneficial effects on the dystrophic muscle, mechanistically acting for the containment of a deregulated nNOS activity.
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spelling doaj.art-b7ff9f68b26348499c510962849700662023-11-18T09:02:35ZengMDPI AGAntioxidants2076-39212023-05-01126118110.3390/antiox12061181Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein LevelsLuisa Gorza0Elena Germinario1Maurizio Vitadello2Irene Guerra3Federica De Majo4Francesca Gasparella5Paolo Caliceti6Libero Vitiello7Daniela Danieli-Betto8Department of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biology, University of Padova, 35131 Padova, ItalyDepartment of Pharmaceutical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biology, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyThe vegetal polyphenol curcumin displays beneficial effects against skeletal muscle derangement induced by oxidative stress, disuse or aging. Since oxidative stress and inflammation are involved in the progression of muscle dystrophy, the effects of curcumin administration were investigated in the diaphragm of <i>mdx</i> mice injected intraperitoneally or subcutaneously with curcumin for 4–12–24 weeks. Curcumin treatment independently of the way and duration of administration (i) ameliorated myofiber maturation index without affecting myofiber necrosis, inflammation and degree of fibrosis; (ii) counteracted the decrease in type 2X and 2B fiber percentage; (iii) increased about 30% both twitch and tetanic tensions of diaphragm strips; (iv) reduced myosin nitrotyrosination and tropomyosin oxidation; (v) acted on two opposite nNOS regulators by decreasing active AMP-Kinase and increasing SERCA1 protein levels, the latter effect being detectable also in myotube cultures from <i>mdx</i> satellite cells. Interestingly, increased contractility, decreased myosin nitrotyrosination and SERCA1 upregulation were also detectable in the <i>mdx</i> diaphragm after a 4-week administration of the NOS inhibitor 7-Nitroindazole, and were not improved further by a combined treatment. In conclusion, curcumin has beneficial effects on the dystrophic muscle, mechanistically acting for the containment of a deregulated nNOS activity.https://www.mdpi.com/2076-3921/12/6/1181curcuminmuscle dystrophynNOSnitrotyrosinenitrosative stressoxidative stress
spellingShingle Luisa Gorza
Elena Germinario
Maurizio Vitadello
Irene Guerra
Federica De Majo
Francesca Gasparella
Paolo Caliceti
Libero Vitiello
Daniela Danieli-Betto
Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
Antioxidants
curcumin
muscle dystrophy
nNOS
nitrotyrosine
nitrosative stress
oxidative stress
title Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
title_full Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
title_fullStr Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
title_full_unstemmed Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
title_short Curcumin Administration Improves Force of <i>mdx</i> Dystrophic Diaphragm by Acting on Fiber-Type Composition, Myosin Nitrotyrosination and SERCA1 Protein Levels
title_sort curcumin administration improves force of i mdx i dystrophic diaphragm by acting on fiber type composition myosin nitrotyrosination and serca1 protein levels
topic curcumin
muscle dystrophy
nNOS
nitrotyrosine
nitrosative stress
oxidative stress
url https://www.mdpi.com/2076-3921/12/6/1181
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