More than three decades ago, researchers first observed that prior exposure of cells to a sublethal stimulus (e.g., heat) provided a protective effect in the face of a subsequent lethal challenge (1). This phenomenon, termed thermotolerance, was later shown to be associated with the selective synthesis of several cellular proteins, called heat shock proteins (1, 2). Virtually all living organisms display this characteristic pattern of protein synthesis to diverse stimuli including alcohols, free radicals, glucose starvation, heavy metals, hypoxia, fevers and inflammation. Thus, heat-shock proteins are now more commonly called stress proteins (2,3). This editorial will first present an overview of the biological roles of several classes of stress proteins and will consider the increasingly persuasive evidence of their potential clinical relevance in aging, cancer, cardiovascular disease and autoimmunity (3).
Stress proteins represent a large multigene family of intracellular proteins that range in molecular size from 10 to 150 kD and show remarkable conservation from the simplest unicellular organism to higher eukaryotes, in support of their fundamental roles in biological systems throughout evolution (3). The most widely studied and abundant are the 70-kD stress protein (70-kD heat-shock protein, or Hsp70) family, whose members comprise the 68-to 78-kD proteins. A further distinction is made between those stress proteins expressed normally or constitutively in unstressed cells (Hsc7O) and those that are rapidly induced in stress conditions (Hsp70). In general, they appear to serve as catalysts for protein folding; several Hsps possess ATPase activity that may facilitate their role as molecular chaperones to assure correct folding, assembly and oligomerization of substrate polypeptides (4).
Another family that has received particular attention and was investigated by Jorge et al. in the November issue of HEPATOLOGY (31, is the Hsp9O group of molecular chaperones (5). Studies of the mechanisms of steroid receptor/hormone action have uncovered a pivotal role of the Hsp9O stress proteins in cell regu-I.J. Benjamin is the recipient of an American Federation of Clinical Research