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

Agostini, Francesco and Dalla Libera, Luciano and Rittweger, Jörn and Mazzucco, Sara and Jurdana, Mihaela and Mekjavic, Igor and Pisot, Rado and Gorza, Luisa and Narici, Marco and Biolo, Gianni (2010) Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach. The Journal of Physiology, 588 (24), pp. 5089-5104. ISSN 0022-3751.

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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 ([2H2]glycine and [15N]glycine) approach based on evaluation of steady-state precursor incorporation in product. The correlations between the traditional (multiple-samples, one-tracer) and new (one-sample, double-tracer infusion) methods were analysed in erythrocytes by Passing–Bablok and Altman–Bland tests. 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 aswell as to compensatory activation of the glutathione system.

Document Type:Article
Title:Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach
AuthorsInstitution or Email of Authors
Agostini, FrancescoUniversity of Trieste
Dalla Libera, LucianoUniversity of Padova
Rittweger, Jörnjoern.rittweger@dlr.de
Mazzucco, SaraUniversity of Trieste
Jurdana, MihaelaUniversity of Primorska
Mekjavic, IgorJozef Stefan Institute
Pisot, RadoUniversity of Primorska
Gorza, LuisaUniversity of Padova
Narici, MarcoManchester Metropolitan University
Biolo, GianniUniversity of Trieste
Journal or Publication Title:The Journal of Physiology
Refereed publication:Yes
In ISI Web of Science:Yes
Page Range:pp. 5089-5104
Keywords:Bed rest, muscle atrophy
HGF - Research field:Aeronautics, Space and Transport (old)
HGF - Program:Space (old)
HGF - Program Themes:W FR - Forschung unter Weltraumbedingungen (old)
DLR - Research area:Space
DLR - Program:W FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):W - Vorhaben Integrative Studien (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Space Physiology
Deposited By: Jörn Rittweger
Deposited On:09 Feb 2011 11:01
Last Modified:12 Dec 2013 21:13

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