Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice

小鼠实验性脓毒症期间运动肌和呼吸肌中 Akt-mTOR、泛素蛋白酶体和自噬溶酶体通路的调节

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作者:Jérome Morel, Jean-Charles Palao, Josiane Castells, Marine Desgeorges, Thierry Busso, Serge Molliex, Vanessa Jahnke, Peggy Del Carmine, Julien Gondin, David Arnould, Anne Cécile Durieux, Damien Freyssenet

Abstract

Sepsis induced loss of muscle mass and function contributes to promote physical inactivity and disability in patients. In this experimental study, mice were sacrificed 1, 4, or 7 days after cecal ligation and puncture (CLP) or sham surgery. When compared with diaphragm, locomotor muscles were more prone to sepsis-induced muscle mass loss. This could be attributed to a greater activation of ubiquitin-proteasome system and an increased myostatin expression. Thus, this study strongly suggests that the contractile activity pattern of diaphragm muscle confers resistance to atrophy compared to the locomotor gastrocnemius muscle. These data also suggest that a strategy aimed at preventing the activation of catabolic pathways and preserving spontaneous activity would be of interest for the treatment of patients with sepsis-induced neuromyopathy.

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