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The responsiveness of regenerated soleus muscle to pharmacological calcineurin inhibition
Author(s) -
Koulmann Nathalie,
Sanchez Hervé,
N'Guessan Benoît,
Chapot Rachel,
Serrurier Bernard,
Peinnequin André,
VenturaClapier Renée,
Bigard Xavier
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20643
Subject(s) - calcineurin , medicine , endocrinology , gene isoform , in vivo , soleus muscle , biology , downregulation and upregulation , messenger rna , skeletal muscle , chemistry , biochemistry , transplantation , gene , microbiology and biotechnology
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 · 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‐Iβ toward MHC‐IIA. Immunohistochemical analysis showed that MHC‐IIA was often co‐expressed with MHC‐Iβ within myofibers of intact muscles, whereas it was mainly expressed within pure fast fibers of regenerated muscles. MHC‐Iβ 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. © 2006 Wiley‐Liss, Inc.