title: A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle.
abstract: It is presently unknown whether oxidative stress increases in disused skeletal muscle in humans. Markers of oxidative stress were investigated in biopsies from the vastus lateralis muscle, collected from healthy subjects before [time 0 (T0)], after 1 wk (T8), and after 5 wk (T35) of bed rest. An 18% decrease in fiber cross-sectional area was detected in T35 biopsies (P<0.05). Carbonylation of muscle proteins significantly increased about twofold at T35 (P<0.02) and correlated positively with the decrease in fiber cross-sectional area (P=0.04). Conversely, T8 biopsies showed a significant increase in protein levels of heme oxygenase-1 and glucose-regulated protein-75 (Grp75)/mitochondrial heat shock protein-70, two stress proteins involved in the antioxidant defense (P<0.05). Heme oxygenase-1 increase, which involved a larger proportion of slow fibers compared with T0, appeared blunted in T35 biopsies. Grp75 protein level increased threefold in T8 biopsies and localized especially in slow fibers (P<0.025), to decrease significantly in T35 biopsies (P<0.05). Percent change in Grp75 levels positively correlated with fiber cross-sectional area (P=0.01). Parallel investigations on rat soleus muscles, performed after 1-15 days of hindlimb suspension, showed that Grp75 protein levels significantly increased after 24 h of unloading (P = 0.02), i.e., before statistically significant evidence of muscle atrophy, to decrease thereafter in relation to the degree of muscle atrophy (P=0.03). Therefore, in humans as in rodents, disuse muscle atrophy is characterized by increased protein carbonylation and by the blunting of the antioxidant stress response evoked by disuse.
authors.affiliation: Consiglio Nazionale delle Ricerche-Institute for Neuroscience, Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35121 Padova, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Dalla Libera
authors.forename: Barbara
authors.initials: B
authors.lastname: Ravara
authors.forename: Valerio
authors.initials: V
authors.lastname: Gobbo
authors.forename: Elena
authors.initials: E
authors.lastname: Tarricone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Vitadello
authors.forename: Gianni
authors.initials: G
authors.lastname: Biolo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vescovo
authors.forename: Luisa
authors.initials: L
authors.lastname: Gorza
mesh_terms: D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001510:Bed Rest; D001706:Biopsy; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D019417:Hindlimb Suspension; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D050050:Protein Carbonylation; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D055815:Young Adult
chemical_list: D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1