Cross-talk between TRPC-1, mTOR, PGC-1 alpha and PPAR delta in the dystrophic muscle cells treated with tempol

Author(s):Show less -

da Rocha, Guilherme Luiz ; Rupcic, Ian Feller ; Mizobuti, Daniela Sayuri ; Hermes, Tulio de Almeida ; Covatti, Caroline ; Mariano da Silva, Heloina Nathallie ; Araujo, Hygor Nunes ; de Lourenco, Caroline Caramano ; Silveira, Leonardo Dos Reis ; Leite Pereira, Elaine Cristina ; Minatel, Elaine

• Document type: Journal article
• Source: Free Radical Research; v. N/A, p. 13-pg., 2022-05-11.

Abstract

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; H2O2 and O-2(center dot-) 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-1 alpha and PPAR delta 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-1 alpha and PPAR delta. (AU)

• FAPESP's process: 17/01638-0 - TEMPOL: POTENTIAL ANTIOXIDANT THERAPY FOR DYSTROPHIC MUSCULAR FIBERS
• Grantee: Elaine Minatel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/25010-1 - Comparative morphological study between the effects of vitamin E and prednisolone in the treatment of muscular dystrophic fibers of mdx mice
• Grantee: Ian Feller Rupcic
• Support Opportunities: Scholarships in Brazil - Scientific Initiation