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Am J Physiol Endocrinol Metab 277: E26-E32, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 1, E26-E32, July 1999

Cytochrome c transcriptional activation and mRNA stability during contractile activity in skeletal muscle

Damien Freyssenet1, Michael K. Connor1, Mark Takahashi2, and David A. Hood1,2

1 Department of Biology and 2 Department of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3

We evaluated contractile activity-induced alterations in cytochrome c transcriptional activation and mRNA stability with unilateral chronic stimulation (10 Hz, 3 h/day) of the rat tibialis anterior (TA) muscle for 1, 2, 3, 4, 5, and 7 days (n = 3-11/group). Transcriptional activation was assessed by direct plasmid DNA injection into the TA with a chloramphenicol acetyltransferase (CAT) reporter gene linked to 326 bp of the cytochrome c promoter. Cytochrome c mRNA in stimulated muscles increased by 1.3- to 1.7-fold above control between 1 and 7 days. Cytochrome c protein was increased after 5 days of stimulation to reach levels that were 1.9-fold higher than control by 7 days. Cytochrome c mRNA stability, determined with an in vitro decay assay, was greater in stimulated TA than in control between 2 and 4 days, likely mediated by the induction of a cytosolic factor. In contrast, cytochrome c transcriptional activation was elevated only after 5 days of stimulation when mRNA stability had returned to control levels. Thus the contractile activity-induced increase in cytochrome c mRNA was due to an early increase in mRNA stability, followed by an elevation in transcriptional activation, leading to an eventual increase in cytochrome c protein levels.

cell-free messenger ribonucleic acid decay; chronic stimulation; direct gene injection; mitochondrial biogenesis


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