Clinical implications of the stress response.

The heat shock response, first observed in Drosophila melano- gaster over thirty years ago, provided investigators a relatively simple way to study rapid changes in gene expression. Simply raising the temperature of Drosophila above its physiologic norm resulted in the decreased expression of those genes which were active before the temperature shock and the increased expression of genes encoding a group of proteins referred to as the heat shock proteins (hsp's).' Over the last 30 years similar changes in gene expression following relevant temperature shocks have been observed in cells from all organisms, be they derived from bacteria, plants, yeast, or mammals. Moreover, the heat shock proteins from various organisms appear highly conserved with respect to their primary structure, mode of regulation, and biochemical function. In addition to heat shock treat- ment, many other types of metabolic insults including exposure to heavy metals, amino acid analogs, different metabolic poisons as well as a variety of relevant insults in vivo (e.g., isch- emia/reperfusion) also elicit increased expression of the hsp's. Accordingly, many investigators now refer to the response more generally as the stress response, and the proteins whose expression increases, the stress proteins.