Cross-talk between TRPC-1, mTOR, PGC-1α and PPARδ in the dystrophic muscle cells treated with tempol

• Published in: Free radical research Vol. 56; no. 3-4; pp. 245 - 257
• Main Authors: Rocha, Guilherme Luiz da, Rupcic, Ian Feller, Mizobuti, Daniela Sayuri, Hermes, Túlio de Almeida, Covatti, Caroline, Silva, Heloina Nathalliê Mariano da, Araujo, Hygor Nunes, Lourenço, Caroline Caramano de, Silveira, Leonardo dos Reis, Pereira, Elaine Cristina Leite, Minatel, Elaine
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.04.2022
• Subjects: calcium channels; Dystrophic muscle cells; mitochondrial biogenesis; muscle cell differentiation; tempol; Dystrophic muscle cells; muscle cell differentiation; tempol; mitochondrial biogenesis; calcium channels
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715762.2022.2074842

Background Ca2+ dysregulation and oxidative damage appear to have a central role in Duchenne muscular dystrophy (DMD) progression. The current study provides muscle cell-specific insights into the effect of Tempol on the TRPC 1 channel; on the positive and negative regulators of muscle cell differentiation; on the antioxidant enzymatic system; on the activators of mitochondrial biogenesis; and on the inflammatory process in the dystrophic primary muscle cells in culture. Methods: Mdx myotubes were treated with Tempol (5 mM) for 24 h. Untreated mdx myotubes and C57BL/10 myotubes were used as controls. Results: The Trypan Blue, MTT and Live/Dead Cell assays showed that Tempol (5 mM) presented no cytotoxic effect on the dystrophic muscle cells. The Tempol treated-mdx muscle cells showed significantly lower levels in the fluorescence intensity of intracellular calcium; TRPC-1 channel; MyoD; H 2 O 2 and O 2 *− production; 4-HNE levels; SOD2, CAT and GPx levels; and TNF levels. On the other hand, SOD, CAT and GR mRNA relative expression were significantly higher in Tempol treated-mdx muscle cells. In addition, higher levels of Myogenin, MHC-Slow, mTOR, PGC-1α and PPARδ were also observed in Tempol treated-mdx muscle cells. Conclusion: Our findings demonstrated that Tempol decreased intracellular calcium and oxidative stress in primary dystrophic muscle cells, promoting a cross-talk between TRPC-1, mTOR, PGC-1α and PPARδ.