Role of Oxidized Protein Repair in Human Skeletal Muscle

Sofia Lourenço; Capucine Trollet; S Butler-Browne Gillian; Bertrand Friguet; Isabelle Petropoulos

doi:10.1016/j.freeradbiomed.2014.10.787

Role of Oxidized Protein Repair in Human Skeletal Muscle

Free Radic Biol Med. 2014 Oct:75 Suppl 1:S39. doi: 10.1016/j.freeradbiomed.2014.10.787. Epub 2014 Dec 10.

Authors

Sofia Lourenço¹, Capucine Trollet², S Butler-Browne Gillian², Bertrand Friguet³, Isabelle Petropoulos³

Affiliations

¹ Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR-8256, Biological Adaptation and Ageing, ERL INSERM U1164, Paris, France. Electronic address: sofia.lourenco@snv.jussieu.fr.
² Sorbonne Universités, UPMC Univ Paris 06, UM76, INSERM U974, Institut de Myologie, CNRS FRE3617, 47 bd de l'Hôpital, 75013 Paris, France.
³ Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR-8256, Biological Adaptation and Ageing, ERL INSERM U1164, Paris, France.

PMID: 26461361
DOI: 10.1016/j.freeradbiomed.2014.10.787

Abstract

There is now increasing evidence that reactive oxygen species (ROS) are signalling molecules that regulate growth, differentiation, proliferation and apoptosis, at least in physiological concentration. However, when ROS levels overcome the capacity of cellular antioxidant systems, they damage cellular components such as nucleic acids, lipids and in particular proteins, inflicting alterations to cell structure and function. Oxidation of sulfur-containing aminoacids, like cysteine and methionine, within proteins, can be repaired by specific enzymatic systems. Indeed methionine sulfoxide is catalytically reduced back to methionine by the methionine sulfoxide reductase (Msr) system. We showed that this Msr system is involved in cellular protection against oxidative stress by preventing apoptosis and limiting irreversible protein oxidative damage. Furthermore, it has been demonstrated that the Msr system is no longer efficient during ageing and senescence as well as that Msr modulates longevity in animal models. In this work we analysed Msr expression in human skeletal muscle. We showed, using both primary and immortalized skeletal muscle cell lines, that the expression of the Msr system increases during differentiation, suggesting a role of this antioxidant system on myofibres formation. Since myoblasts senescence associated with less differentiation capacity and an abnormal production of ROS have been observed in some muscular dystrophies, we wondered about the state of the Msr system in late-onset myopathies, such as oculopharyngeal muscular dystrophy (OPMD). In OPMD we confirmed, at the transcription level, an increased expression of Msr with differentiation, both on immortalized and primary cell cultures, similarly to what we observed on control cell lines. Our aim is to characterize for the first time the role of a major oxidized protein repair system (Msr) in human skeletal muscle homeostasis and, in particular, in myotubes protection during oxidative stress conditions.