THE EFFECT OF ENDOTOXIN ON SKELETAL-MUSCLE PROTEIN GENE-EXPRESSION INTHE RAT

Sepsis is associated with net breakdown of skeletal muscle protein, me diated partly by reduced rates of muscle protein synthesis. This study investigated the role of altered gene expression for specific muscle proteins in mediating reduced protein synthesis in a rat model of acut e severe sepsis. Adult rats were given a single sublethal intraperiton eal dose of endotoxin (bacterial lipopolysaccharide), Protein, RNA and DNA contents of muscle were meaured and changes in expression of mRNA in tibialis anterior and extensor digitorum longus muscles were detec ted by quantification of Northern blots at 6, 24, 48 and 72 hr after e ndotoxin and in animals starved for 24 hr, Results showed that at 24 h r after endotoxin there was loss of about 14% of muscle protein conten t, No reduction in mRNA was found at any time point for beta-myosin he avy chain (MHC), fast-MHC, alpha-actin, skeletal muscle troponin or ca rbonic anhydrase III (CA III); rather, at 48 hr there was increased ex pression of beta-MHC (224 +/- 123% control) and CA III (202 +/- 56%). Blocking TNF-alpha by pre-treatment with a monoclonal antibody did not appear to influence this. Total RNA content of muscle was reduced to 67% of the control values 24 hr after LPS, although this was no differ ent to pair-fed animals starved for 24 hr, It is concluded that reduce d protein synthesis in skeletal muscle in early acute sepsis is not pr imarily associated with reduced muscle protein gene expression. Copyri ght (C) 1996 Elsevier Science Ltd.