The coordinated cellular responses to physiological stress are known to be effected in part by the activation of heat-shock factor 1, a transcriptional activator protein capable of binding to, and inducing transcription from genes containing heat shock elements. Other stress responsive signal transduction pathways also exist including the stress activated protein kinase cascade that regulates the activity of the transcription factor AP1. We have examined the expression of the low molecular stress proteins, heat shock protein 27 and alpha B-crystallin in astrocytes in response to physiological stress of different types and asked what component of this induction is effected at the transcriptional level and whether activation of heat shock factor 1 and AP1 might account for these events. We have found that stress regulated induction of alpha B-crystallin has a strong transcriptional component and that it may be effected by at least two different transcriptional mechanisms. In one set of phenomena, represented here by cadmium exposure, alpha B-crystallin and heat shock protein 27 are coordinately regulated and this occurs in the presence of activated heat shock factor 1. In the second series of phenomena, represented here by hypertonic stress, alpha B-crystallin is induced in the absence of heat shock factor activation and in the absence of any corresponding change in heat shock protein 27 expression. Although hypertonic stress does activate an AP1-like binding activity, the AP1 consensus binding site in the alpha B-crystallin promoter does not appear to be a target for this hypertonic stress inducible activity. These data suggest that the hypertonic stress response is effected through a heat shock factor independent mechanism and that hypertonic stress regulated induction of alpha B-crystallin does not directly depend on the SAPK pathway and AP1 activity.
978Characterization of the novel mutant A78T-HERG from a long QT syndrome type2 patient: Instability of the mutant protein and stabilization by heat shock protein family and heat shock factor-1
