Heat shock proteins (HSPs), a group of highly conserved proteins induced in response to a variety of cellular stresses, appear to be critical for maintaining cellular homeostasis. Previously we demonstrated that restraint or immobilization stress elicits the induction of HSP70 mRNA and protein selectively in the adrenal gland and vasculature of rats. In both tissues this stress-induced HSP70 expression was found to be linked to the activation of the neuroendocrine response to stress and was attenuated with age. Preliminary evidence also suggested that it was mediated through the activation of one or more transcription factors known as heat shock transcription factor(HSF), which binds to a DNA sequence, the HSE, in the promoter of HSP genes resulting in their transcriptional activation. We have extended our previous studies to show that adrenal extracts obtained from aged rats show a reduced level of HSE-binding activity (indicative of less activated HSF) compared to those of young animals. Using antibodies to distinct members of the HSF family we have shown that the HSF that mediates the response is HSF1. We have compared the quantities of HSF1 protein in extracts of old and young rats and found them to be similar. These findings suggest that the differences in HSP70 expression observed between young and aged rats are not due to an age-related decline in levels of the transcription factor, but rather, are likely due to differences in a step in the signal transduction pathway leading to activation of HSF1 to a DNA binding state. We have developed a cross-transplantation model to address the question of whether the aging process is inherent to the aorta or whether it is the environment in which the aorta resides that is responsible for the age-associated decline in stress-induced HSP70 expression in this tissue. Results obtained thus far indicate that when aortas of aged animals are transplanted to young animals, they show enhanced expression of HSP70 mRNA relative to native aortas of aged animals. In contrast, when young aortas are transplanted to aged animals, they show a marked attenuation in the response to restraint. Thus, the environment in which the aorta resides is a major factor in determining the level of HSP70 expression seen in vessels of stressed animals.
