Mammalian stress proteins HSP70 and HSP28 coinduced by nicotine and either ethanol or heat.
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.
Hahn
G M
GM
Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468.
Shiu
E C
EC
Auger
E A
EA
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D015151:Immunoblotting; D009538:Nicotine / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism
D006360:Heat-Shock Proteins; D014157:Transcription Factors; D000431:Ethanol; D009538:Nicotine