Myogenic and nonmyogenic cells differentially express proteinases, Hsc/Hsp70, and BAG-1 during skeletal muscle regeneration.

Stéphanie Duguez, Marie-Catherine Le Bihan, Dominique Gouttefangeas, Léonard Féasson, Damien Freyssenet

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52 Citations (Scopus)


Skeletal muscle has a remarkable capacity to regenerate after injury. To determine whether changes in the expression of proteinases, 73-kDa constitutive heat shock cognate protein (Hsc70) and stress-inducible 72-kDa heat shock protein (Hsp70) (Hsc/Hsp70), and Bcl-2-associated gene product-1 (BAG-1) contribute to the remodeling response of muscle tissue, 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 postinjection (n = 5-7/group). The immunohistochemical analysis of desmin, alpha-actin, and developmental/neonatal myosin heavy chain expressions indicated the presence of myoblasts (days 3-7), inflammatory cells (days 3-7), degenerating myofibers (days 3-7), regenerating myofibers (days 5-10), and growing mature myofibers (days 10-21) in regenerating muscles. Our biochemical analysis documented profound adaptations in proteolytic metabolism characterized by significant increases in the enzyme activities of matrix metalloproteinases 2 and 9 and plasminogen activators (days 3-14), calpains 1 and 2 (days 3-7), cathepsins B and L(days 3-10), and proteasome (days 3-14). Proteasome activity was strongly correlated with proliferating cell nuclear antigen protein level, suggesting that proteasome played a key role in myoblast proliferation. The expression pattern of BAG-1, a regulatory cofactor of Hsc/Hsp70 at the interface between protein folding and proteasomal proteolysis, did not corroborate the changes in proteasome enzyme activity, suggesting that BAG-1 may promote other functions, such as the folding capacity of Hsc/Hsp70. Altogether, the diversity of functions attributed to proteinases in the present study was strongly supported by the relative changes in the proportion of myogenic and nonmyogenic cells over the time course of regeneration.
Original languageEnglish
Pages (from-to)E206-E215
JournalAmerican journal of physiology. Endocrinology and metabolism
Issue number1
Publication statusPublished (in print/issue) - 1 Jul 2003


  • heat shock cognate protein 70
  • heat shock protein 70
  • Bcl-2- associated gene product-1
  • chaperone
  • immunohistochemis- try
  • matrix metalloproteinases
  • myogenesis
  • proliferating cell nuclear antigen


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