Cells exposed to a variety of stresses such as heat or
ethanol respond by increasing their rate of synthesis of a set of
proteins termed
heat shock proteins (HSP). These
proteins then appear to offer protection against the stressor and many other insults. The HSP also play important roles in unstressed cells. They are involved in the regulation of the cell cycle and during specific stages in the development of organisms. Exposure to stress during development (e.g., in pupal stages of insects or during gestation in mammals) leads to
birth defects that are specific to the timing of the stress. It has been hypothesized that the ill-timed induction of HSP is responsible for this phenomenon. Epidemiological studies in humans have related teratogenic events to maternal exposures to
hyperthermia or
ethanol during pregnancy. The rate of alcohol-induced
birth defects is greatly enhanced by smoking, suggesting a role for
nicotine.
Nicotine by itself, however, is said not to induce HSP. We hypothesized that
nicotine may act as a coinducer (or facilitator) of stress responses. This possibility we tested on three levels: protection against heat (thermotolerance), induction of specific HSP, and binding of the
heat shock transcription factor to the heat shock
element. Each of these tests showed clearly that
nicotine does indeed play such a role. This places
nicotine in a novel position; to date, no other coinducers of stress responses have been reported. Our results may offer an explanation for the epidemiological data cited earlier.