Abstract
Sepsis elicits skeletal muscle atrophy as a result of decreased total protein synthesis and/or increased total protein degradation. It is unknown how and whether sepsis differentially affects the expression of specific myofibrillar proteins in respiratory and limb muscles. In this study, we measured the effects of sepsis myofibrillar mRNAs and their corresponding protein levels in the diaphragm (DIA) and tibialis anterior (TA) muscles in a murine cecal ligation and perforation (CLP) model of sepsis. Male mice (C57/BL6j) underwent CLP-induced sepsis. Sham-operated mice were subjected to the same surgical procedures, except for CLP. Mice were euthanized 24, 48, or 96 h postsurgery. Transcript and protein levels of autophagy-related genes, ubiquitin E3 ligases, and several myofibrillar genes were quantified. Sepsis elicited transient fiber atrophy in the DIA and prolonged atrophy in the TA. Atrophy was coincident with increased autophagy and ubiquitin E3 ligase expression. Myosin heavy chain isoforms decreased at 24 h in the DIA and across the time-course in the TA, myosin light chain isoforms decreased across the time-course in both muscles, and troponins T and C as well as tropomyosin decreased after 24 and 48 h in both the DIA and TA. α-Actin and troponin I were unaffected by sepsis. Sepsis-induced decreases in myofibrillar protein levels coincided with decreased mRNA expressions of these proteins, suggesting that transcriptional inhibition is involved. We hypothesize that sepsis-induced muscle atrophy is mediated by decreased transcription and enhanced degradation of specific myofibrillar proteins, including myosin heavy and light chains, troponin C, troponin T, and tropomyosin.