Abstract

<b>Background &amp; Aims:</b> Sepsis triggers skeletal muscle contractile dysfunction and fiber atrophy. In this study, we evaluated the differential effects of sepsis on the ventilatory and limb muscle fiber atrophy and tested whether sepsis-induced fiber atrophy is the result of decreased expression of various myofilament proteins. <b>Methods:</b> Adult C57/Bl6 mice underwent cecal ligation and perforation (CLP group) to induce severe sepsis. Group 2 underwent sham surgical procedure (Sham group). The diaphragm (DIA) and tibialis anterior (TA) muscles were examined after 24, 48 and 96h of the surgical procedure. Fiber atrophy was quantified from muscle fiber cross sectional areas. Myofilament proteins were quantified both at the mRNA and protein levels using qPCR and immunoblotting. <b>Results:</b> Sepsis triggered transient DIA fiber atrophy (24h) whereas more persistent fiber atrophy was evident in the TA (24, 48 and 96h). In addition, mRNA and protein levels of Myosin Heavy Chain (MyHC), Myosin Light Chain (MyLC), Troponin-T, Troponin-C and Tropomyosin were strongly decreased both in the DIA and TA by sepsis while α-Actin and Troponin-I levels were not influenced by sepsis. The decrease in MyHC and MyLC protein contents was sustained even after 96h of sepsis while the decline in Troponin-T, Troponin-I, Troponin-C and Tropomyosin mRNA and protein levels was restricted to 24 and 48h after induction of sepsis. <b>Conclusions:</b> Sepsis triggers more severe and sustained muscle atrophy in limb muscles than in the diaphragm. Sepsis-induced atrophy is caused by decreased contractile and regulatory myofilament protein levels as a result of both increased proteolysis and decreased transcription.

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