HEAT-SHOCK RESPONSE - PATHOPHYSIOLOGICAL IMPLICATIONS

All organisms exposed to environmental stress conditions share a commo n molecular response characterized by a dramatic change in the pattern of gene expression followed by an elevated synthesis of heat shock or stress proteins. These proteins function as molecular chaperones to p rotect cells from environmental stress damage by binding to partially denatured proteins, dissociating protein aggregates, and regulating th e correct folding and intracellular translocation of newly synthesized polypeptides. Accumulating evidence supports a role for heat shock pr oteins in a number of disease states of which inflammatory reactions a nd ischaema provide the best studied examples. The inducible heat shoc k response involves transcriptional gene activation mediated by specif ic regulatory proteins called heat shock transcription factors, which bind to the promoter of heat shock genes in a sequence-specific manner , However, the signalling pathways leading to the activation of these transcription factors need to be characterized in more detail to be ab le to understand the role, cause, or consequence, of heat shock protei ns in human diseases, This review presents recent progress in unravell ing the regulation of heat shock gene expression in cells subjected to heat or other forms of stress, By using inflammatory responses and my ocardial ischaema as examples, the putative use of heat shock proteins are discussed as targets for future therapeutic applications.