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Journal Articles Journal of Cellular Physiology Year : 2006

The responsiveness of regenerated soleus muscle to pharmacological calcineurin inhibition.

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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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Dates and versions

inserm-00410547 , version 1 (10-09-2009)

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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, 2006, 208 (1), pp.116-22. ⟨10.1002/jcp.20643⟩. ⟨inserm-00410547⟩

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