title: Myogenic and nonmyogenic cells differentially express proteinases, Hsc/Hsp70, and BAG-1 during skeletal muscle regeneration.
abstract: 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.
authors.affiliation: Laboratoire de Physiologie, Groupe Physiologie et Physiopathologie de l'Exercice et Handicap, Groupement d'Intérêt Public-Exercise Sport Santé, Faculté de Médecine, Saint-Etienne, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Duguez
authors.forename: Marie-Catherine Le
authors.initials: MC
authors.lastname: Bihan
authors.forename: Dominique
authors.initials: D
authors.lastname: Gouttefangeas
authors.forename: Léonard
authors.initials: L
authors.lastname: Féasson
authors.forename: Damien
authors.initials: D
authors.lastname: Freyssenet
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002154:Calpain / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis*; D002401:Cathepsin B / Q000096:biosynthesis; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins; D003893:Desmin / Q000096:biosynthesis / Q000235:genetics; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000302:isolation & purification; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D000199:Actins; C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D003893:Desmin; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494373:Hspa8 protein, rat; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D014157:Transcription Factors; D000135:Acid Phosphatase; D002403:Cathepsins; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D046988:Proteasome Endopeptidase Complex; D018995:Myosin Heavy Chains