AI Article Synopsis
- - The study explores how slow-twitch muscle fibers rely on mitochondrial activity, highlighting a connection between muscle-specific protein expression and mitochondrial development, particularly focusing on the role of PGC-1alpha.
- - Researchers utilized gene electrotransfer to show that introducing PGC-1alpha into rat muscle significantly boosts the activity of the cytochrome c promoter and also affects the MyoD promoter, but not the fast troponin I promoter.
- - The findings indicate that calcineurin A (CnA) and calcium/calmodulin kinase IV (CaMKIV) can activate the PGC-1alpha promoter, suggesting that CnA plays a key role in regulating the expression of certain muscle proteins linked to mitochondrial function.
Article Abstract
In skeletal muscle, slow-twitch fibers are highly dependent on mitochondrial oxidative metabolism suggesting the existence of common regulatory pathways in the control of slow muscle-specific protein expression and mitochondrial biogenesis. In this study, we determined whether peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) could transactivate promoters of nuclear-encoded mitochondrial protein (cytochrome c) and muscle-specific proteins (fast troponin I, MyoD). We also investigated if calcineurin A (CnA) and calcium/calmodulin kinase IV (CaMKIV) were involved in the regulation of PGC-1alpha and cytochrome c promoter. For this purpose, we took advantage of the gene electrotransfer technique, which allows acute expression of a gene of interest. Electrotransfer of a PGC-1alpha expression vector into rat Tibialis anterior muscle induced a strong transactivation of cytochrome c promoter (P < 0.001) independent of nuclear respiratory factor 1. PGC-1alpha gene electrotransfer did not transactivate fast troponin I promoter, whereas it did transactivate MyoD promoter (P < 0.05). Finally, whereas electrotransfers of CnA or CaMKIV expression vectors transactivated PGC-1alpha promoter (P < 0.001), gene electrotransfer of CaMKIV was only able to transactivate cytochrome c promoter. Taken together, these data suggest that CnA triggers PGC-1alpha promoter transactivation to drive the expression of non-mitochondrial proteins.
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| http://dx.doi.org/10.1007/s00424-007-0206-6 | DOI Listing |
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