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Laboratoire de Physiologie, Groupe Physiologie et Physiopathologie de l'Exercice et du Handicap Groupement d'Intérêt Public-E2S, Faculté de Médecine, 42023 Saint-Etienne, France
Myogenesis requires energy
production for the execution of a number of regulatory and biosynthesis
events. We hypothesized that mitochondrial biogenesis would be
stimulated during skeletal muscle regeneration. Tibialis anterior
muscles of male Sprague-Dawley rats were injected with 0.75%
bupivacaine and removed at 3, 5, 7, 10, 14, 21, or 35 days after
injection (n = 5-7/group). Two main periods
emerged from the histochemical analyses of muscle sections and the
expression of proliferating cell nuclear antigen, desmin, and creatine
phosphokinase: 1) activation/proliferation of satellite
cells (days 3-14) and 2) differentiation
into muscle fibers (days 5-35). The onset of
muscle differentiation was accompanied by a marked stimulation of
mitochondrial biogenesis, as indicated by a nearly fivefold increase in
citrate synthase activity and state 3 rate of respiration between
days 5 and 10. Peroxisome proliferator-activated
receptor-
coactivator-1 (PGC-1) mRNA level and mitochondrial
transcription factor A (mtTFA) protein level peaked on day
10 concurrently with the state 3 rate of respiration. Therefore,
transcriptional activation by PGC-1 and mtTFA may be one of the
mechanisms regulating mitochondrial biogenesis in regenerating skeletal
muscle. Taken together, our results suggest that mitochondrial biogenesis may be an important regulatory event during muscle regeneration.
mitochondrial respiration; muscle precursor cells; myogenesis; peroxisome proliferator-activated receptor- coactivator-1; mitochondrial transcription factor A
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