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The responsiveness of regenerated soleus muscle to pharmacological calcineurin inhibition.

Abstract : The responsiveness of mature regenerated soleus (SOL) muscles to cyclosporin A (CsA) administration was studied in rats. Forty-two days after notexin-induced degeneration of left SOL muscles, rats were treated with CsA (25 mg/kg x day) or vehicle daily for 3 weeks. CsA administration decreased by eightfold the level of transcription of MCIP-1, a well-known calcineurin-induced gene, in intact as well as in regenerated muscles (P < 0.001). In response to CsA-administration we observed a slow-to-fast transition in the MHC profile, more marked in regenerated than in intact muscles (P < 0.05), but mainly restricted to MHC-Ibeta toward MHC-IIA. Immunohistochemical analysis showed that MHC-IIA was often co-expressed with MHC-Ibeta within myofibers of intact muscles, whereas it was mainly expressed within pure fast fibers of regenerated muscles. MHC-Ibeta mRNA levels were lower in regenerated than in intact muscles, but did not change in response to CsA-administration. CsA administration induced a significant increase in MHC-IIA mRNA levels (P < 0.001) similar in both intact and regenerated muscles. Present results suggest that in vivo in intact SOL muscles, calcineurin blocks the upregulation of the MHC-IIA isoform at the transcriptional level. On the other hand, the higher response of regenerated muscles to CsA administration cannot be explained by transcriptional events, and may result from either a more rapid turnover of MHC proteins in regenerated muscles than in intact ones, or translational events. This study further suggests that the developmental history of myofibers could play a role in the adaptability of skeletal muscle to variations in neuromuscular activity.
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Nathalie Koulmann, Hervé Sanchez, Benoît N'Guessan, Rachel Chapot, Bernard Serrurier, et al.. The responsiveness of regenerated soleus muscle to pharmacological calcineurin inhibition.. Journal of Cellular Physiology, Wiley, 2006, 208 (1), pp.116-22. ⟨10.1002/jcp.20643⟩. ⟨inserm-00410547⟩

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