Testosterone induces up-regulation of mitochondrial gene expression in murine C2C12 skeletal muscle cells accompanied by an increase of nuclear respiratory factor-1 and its downstream effectors. (15th January 2020)

• Record Type: Journal Article
• Authors: Pronsato, Lucía; Milanesi, Lorena; Vasconsuelo, Andrea
• Is Part Of: Molecular and cellular endocrinology. Volume 500(2020)
• Publication Date: 2020-01-15
• Subjects: Testosterone -- AR -- NRF-1 -- Tfam -- Mitochondrial biogenesis -- Mitochondrial genes; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.110631
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The reduction in muscle mass and strength with age, sarcopenia, is a prevalent condition among the elderly, linked to skeletal muscle dysfunction and cell apoptosis. We demonstrated that testosterone protects against H2 O2 -induced apoptosis in C2C12 muscle cells. Here, we analyzed the effect of testosterone on mitochondrial gene expression in C2C12 skeletal muscle cells. We found that testosterone increases mRNA expression of genes encoded by mitochondrial DNA, such as NADPH dehydrogenase subunit 1 ( ND1 ), subunit 4 ( ND4 ), cytochrome b ( CytB ), cytochrome c oxidase subunit 1 ( Cox1 ) and subunit 2 ( Cox2 ) in C2C12. Additionally, the hormone induced the expression of the nuclear respiratory factors 1 and 2 ( Nrf-1 and Nrf-2 ), the mitochondrial transcription factors A ( Tfam ) and B2 (TFB2M), and the optic atrophy 1 (OPA1). The simultaneous treatment with testosterone and the androgen receptor antagonist, Flutamide, reduced these effects. H2 O2 -oxidative stress induced treatment, significantly decreased mitochondrial gene expression. Computational analysis revealed that mitochondrial DNA contains specific sequences, which the androgen receptor could recognize and bind, probably taking place a direct regulation of mitochondrial transcription by the receptor. These findings indicate that androgen plays an important role in the regulation of mitochondrial transcription and biogenesis in skeletal muscle. Highlights: Testosterone induces NRF1 and 2, Tfam and TFB2M transcription factors expression. Testosterone upregulates mitochondrial genes that encode MRC proteins. H2 O2 downregulates mitochondrial genes that encode MRC proteins. Testosterone promotes mitochondria preservation by induction of OPA1 expression. Mouse mitochondrial genome contains putative AR binding sites.