Protein synthesis in the heart in vivo, its measurement and patho-physiological alterations

Changes in cardiac protein composition occur in a variety of patho-physiological situations and are usually accompanied by modifications in protein synthesis. Although adjustments in protein synthesis during starvation may be adaptive, the alterations in protein synthesis seen in response to ethanol ingestion may be pathological and an important step in the genesis of alcoholic heart muscle disease. The alterations in heart muscle in hypertension are initially adaptive but in the long term they are deleterious, and involve both transcription and translation. While adequate methods exist for quantifying the amount of mRNA for contractile and non-contractile proteins, such studies of gene-expression provide no dynamic information on the rate at which tissue proteins are lost or accrued. This can only be determined by measuring the rate of protein turnover, i.e. either protein synthesis or protein breakdown. Techniques for directly determining the rates of protein breakdown are limited or involve surgical procedures. Methods for measuring the rate of protein synthesis are described, and are illustrated by their application to the investigation of starvation and ethanol toxicity. In particular, attention is focused on the fact that reliable rates of protein synthesis are obtained only if the specific radioactivity of the precursor at the site of protein synthesis (aminoacyl-tRNA) is assessed.