Overexpression of inducible 70-kDa heat shock protein in mouse attenuates skeletal muscle damage induced by cryolesioning.
Heat shock protein expression is elevated upon exposure to a variety of stresses and limits the extent of stress-induced damage. To investigate the putative role of inducible 70-kDa heat shock protein (HSP70) in skeletal muscle damage and regeneration, soleus and tibialis anterior (TA) muscles from HSP70-overexpressing transgenic mice were subjected to cryolesioning and analyzed after 1, 10, and 21 days. Histological analysis showed that the muscles from both HSP70 and wild-type mice treated with radicicol (a HSP inducer) had decreased necrosis after cryolesioning compared with controls. The decrease in muscle fiber cross-sectional area in both soleus and TA muscles in 10 days postlesioning was attenuated in HSP70 mice compared with wild-type mice. Glutathione peroxidase activity was increased 1 day after cryolesioning in both HSP70 and control mice and remained elevated for up to 21 days. Immunodetection of neuronal cell adhesion molecule (a satellite cell marker) and developmental/neonatal MHC were significantly lower in cryolesioned HSP70-overexpressing mice than in cryolesioned controls. These results suggest that HSP70 protects skeletal muscle against injury and radicicol might be useful as a skeletal muscle protective agent.
Miyabara
Elen H
EH
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Martin
Jody L
JL
Griffin
Tina M
TM
Moriscot
Anselmo S
AS
Mestril
Ruben
R
D000818:Animals; D003452:Cryosurgery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb / Q000033:anatomy & histology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009336:Necrosis; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009929:Organ Size; D051381:Rats
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007783:Lactones; D018942:Macrolides; D019006:Neural Cell Adhesion Molecules; D005979:Glutathione Peroxidase; D018995:Myosin Heavy Chains; C035359:monorden