Diverse forms of stress lead to new patterns of gene expression through a common and essential metabolic pathway

Abstract

Many eukaryotic organisms respond to heat shock by synthesizing new proteins. We examined the possibility that heat shock proteins represent a particular expression of a general response to stress and that, regardless of the nature of the effective stimulus, the same proteins are synthesized. Accordingly, cardiac stress was applied in the intact rat by four methods: banding the ascending aorta, increasing body temperature to 42 degrees C, reducing body temperature to 18 degrees C, and forcing the rat to swim until exhausted. The hearts were then extirpated and analyzed for new mRNA synthesis. The extracted RNA was translated in a cell-free medium containing [35S]methionine. Translation products were resolved by two-dimensional electrophoresis and visualized by autoradiography. Lactic acid concentration in heart tissue was determined enzymatically. The results showed that two new and distinct proteins of Mr 71,000 and isoelectric points of 5.8 and 6.1 were synthesized in hearts stressed by banding and by heating but not in hearts of exhausted swimmers or in animals at reduced body temperatures. There was no significant difference in cardiac lactic acid concentration between control hearts and hearts from swimmers or cold-treated animals. However, there was a 2-fold increase in lactic acid concentration in hearts of rats with banded aortas compared to controls and a 10-fold increase in heat shocked hearts. We conclude that, under conditions in which the energy requirements of the heart are not completely met by aerobic processes, the resultant lactic acidosis creates an intracellular environment that leads to the selective activation of genes, the production of new mRNA, and the synthesis of a typical group of stress proteins.