Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach

Abstract

Oxidative stress is often associated to inactivity-mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers. To assess muscle glutathione synthesis, we applied a novel single-biopsy and double-tracer ( Muscle glutathione absolute synthesis rate increased following bed rest from 5.5 ± 1.1 to 11.0 ± 1.5 mmol (kg wet tissue) −1 day −1 (mean ± s.e.m.; n = 9; P = 0.02) while glutathione concentration failed to change significantly. Bed rest induced vastus lateralis muscle atrophy, as assessed by pennation angle changes measured by ultrasonography (from 18.6 ± 1.0 to 15.3 ± 0.9 deg; P = 0.01) and thickness changes (from 2.3 ± 0.2 to 1.9 ± 0.1 cm; P < 0.001). Moreover, bed rest increased protein oxidative stress, as measured by muscle protein carbonylation changes (from 0.6 ± 0.1 to 1.00 ± 0.1 Oxydized-to-total protein ratio; P < 0.04).In conclusion, we developed in erythrocytes a new minimally invasive method to determine peptide synthesis rate in human tissues. Application of the new method to skeletal muscle suggests that disuse atrophy is associated to oxidative stress induction as well as to compensatory activation of the glutathione system.

Oxidative stress and frailty: A systematic review and synthesis of the best evidence

“…Low physical activity is one of the hallmarks of frailty (18), and has been consistently reported to significantly increase OS in both animal models and humans (13,32). Therefore, a vicious circle may occur between OS and frailty.…”

“…These interacting pathways may contribute to the detrimental effects of OS on muscles, bones, and the immune system (12). Loss of muscle mass and strength may reduce physical activity and thereby contribute to frailty (13).…”

Movilización segura del paciente en estado crítico: una perspectiva desde la fisiatría

“…El glutatión es uno de los principales sistemas antioxidantes estimulados tanto a nivel muscular como sistémico, por la activación de los procesos oxidativos. La tasa de síntesis absoluta de glutatión muscular aumentó tras el reposo en cama, mientras que su concentración no cambió significativamente 31 .…”

Nutritional strategies to counteract muscle atrophy caused by disuse and to improve recovery

“…When reactive oxygen species increase in skeletal muscle, DNA fragmentation, lipid peroxidation and protein oxidation can result, which can lead to apoptosis, depending on the severity of the oxidative stress (69,118,119) . As an example, a large increase in carbonylated protein content was demonstrated in human subjects following 35 d of bed rest (109) . When carbonylated, proteins are preferentially degraded by the 20S proteasome without ubiquitination (120) and there is evidence that these damaged proteins are more efficiently and rapidly scavenged by proteolytic degradation than their non-oxidised forms to avoid accumulation of damaged functional proteins (120 -122) .…”

“…Furthermore, growing evidence suggests that skeletal muscle atrophy is positively correlated with oxidative stress in various situations of muscle disuse (99 -106) despite there being no clear evidence to determine if it is a primary cause or a latter consequence of disuse. This oxidative stress is characterised by an increase in reactive oxygen species in skeletal muscle of both animals (107,108) and humans (106,109) . It has been postulated that this oxidative stress may play an important role in the process of muscle atrophy during disuse (75) .…”