Tumor Necrosis Factor-α Provokes a Hypertrophic Growth Response in Adult Cardiac Myocytes

Abstract

Background Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine with a broad range of concentration-dependent effects. The recent observation that TNF-α is expressed by the cardiac myocyte after certain forms of stress suggests that TNF-α might contribute to the maintenance of normal tissue homeostasis after environmental injury. Accordingly, the purpose of this study was to examine the effects of TNF-α on protein synthesis in cultured adult cardiac myocytes. Methods and Results Cultured adult feline cardiac myocytes were stimulated with 10 to 1000 U/mL TNF-α to examine the effects of this cytokine on the rate of protein synthesis and degradation. Stimulation with TNF-α led to an accelerated rate of general protein synthesis and a time-dependent decrease in protein degradation in adult cardiac myocytes. The specificity of these findings was demonstrated by studies in which the effects of TNF-α on protein synthesis were blocked by a neutralizing anti–TNF-α antibody as well as studies in which TNF-α–co...