Skeletal muscle
atrophy is a common phenomenon during the prolonged muscle disuse caused by cast immobilization, extended aging states,
bed rest, space flight, or other factors. However, the cellular mechanisms of the atrophic process are poorly understood. In this study, we investigated the involvement of
mitogen-activated protein kinase (MAPK) in the expression of muscle-specific RING finger 1 (MuRF1) during
atrophy of the rat gastrocnemius muscle. Histological analysis revealed that cast immobilization induced the
atrophy of the gastrocnemius muscle, with diminution of muscle weight and cross-sectional area after 14 days. Cast immobilization significantly elevated the expression of MuRF1 and the phosphorylation of
p38 MAPK. The
starvation of L6 rat skeletal myoblasts under serum-free conditions induced the phosphorylation of
p38 MAPK and the characteristics typical of cast-immobilized gastrocnemius muscle. The expression of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly attenuated by
SB203580, an inhibitor of
p38 MAPK. Changes in the sizes of L6 myoblasts in response to
starvation were also reversed by their transfection with MuRF1
small interfering RNA or treatment with
SB203580. From these results, we suggest that the expression of MuRF1 in cast-immobilized
atrophy is regulated by
p38 MAPK in rat gastrocnemius muscles.