Cardiac Muscle Protein Gene Expression in the Endotoxin-Treated Rat

Abstract

1. Sepsis is associated with marked changes in cardiac muscle protein synthesis. Such changes may be the result of altered transcription of specific myofibrillar protein mRNAs. 2. In order to investigate myofibrillar protein gene expression, a rat model of sepsis was used. Adult rats were given a single sub-lethal dose of lipopolysaccharide by the intraperitoneal route. At various times thereafter, rats were killed and ventricular muscle was removed. RNA was extracted and transferred to nylon membranes. Changes in expression of mRNA for alpha- and beta-myosin heavy chain, alpha-actin, cardiac troponin C and carbonic anhydrase III were detected by Northern hybridization. 3. After treatment with lipopolysaccharide, mRNA for beta-myosin heavy chain increased to 260% of control values at 24 h and reached a maximum of 310% at 48 h. alpha-Myosin heavy chain mRNA levels fell to 72% of control values at 24 h. mRNA levels for alpha-actin, cardiac troponin C and carbonic anhydrase III remained unchanged. 4. In order to investigate the role of tumour necrosis factor-alpha in this process, some rats were pretreated with monoclonal antibody against tumour necrosis factor-alpha before receiving lipopolysaccharide. Such animals showed an absence of tumour necrosis factor-alpha bioactivity in plasma, but changes in myocardial protein mRNA levels were no different from those seen in animals receiving lipopolysaccharide alone. 5. The reduction in protein synthesis in cardiac muscle in sepsis does not appear to be the result of reduced expression of genes for structural or soluble muscle protein.(ABSTRACT TRUNCATED AT 250 WORDS)