Skeletal muscle atrophy increases cell proliferation in mice gastrocnemius during the first week of hindlimb suspension.
The comprehension of the cellular mechanisms underlying skeletal muscle atrophy has been the aim of several experimental studies. However, the majority of them focused on alterations of the myocytes induced by different experimental conditions yet disregarding the contribution of other cells such as endothelial cells and fibroblasts. In this sense, 70 Charles River CD1 male mice were randomly assigned to seven groups (n=10 per group): control and 6, 12, 24, 48, 72 h and 1 week with respect to the period of hindlimb suspension. Forty-eight hours before sacrifice, the animals were injected with bromodeoxyuridine (BrdU) in order to identify proliferating cells. Immunohistochemistry and south-western blotting techniques were used to evaluate across the whole gastrocnemius muscle BrdU incorporation into the different proliferating cells. The contribution of the apoptotic response was also measured in order to ascertain whether the balance between cell survival and death was preserved. The results observed during 1 week of unloading-induced atrophy evidenced an intense peak of proliferating activity only after 6 h, mainly due to the duplication of satellite cells. Consequently to this unexpected activation of satellite cells, the addition of nuclei to the fibre syncytium was recognized at 12 h of unloading. After 48 h of weightlessness, the proliferating activity observed was largely due to an interstitial fibrosis. According to the apoptotic index profile observed during the analysed unloading period, this general proliferative activity was balanced by apoptosis, which strongly suggests the existence of a regulatory feedback response between anabolic and catabolic events in unloading-induced skeletal muscle atrophy.
Ferreira
Rita
R
CIAFEL, Laboratory of Sport Biochemistry, Faculty of Sports Sciences, University of Porto, Rua Dr. Plácido Costa, 91, 4200, Porto, Portugal. rmferreira@fcdef.up.pt
Neuparth
Maria João
MJ
Ascensão
António
A
Magalhães
José
J
Vitorino
Rui
R
Duarte
José Alberto
JA
Amado
Francisco
F
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000473:pathology; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology; D013997:Time Factors
D011506:Proteins; D004247:DNA; D001973:Bromodeoxyuridine