Mammalian stress proteins HSP70 and HSP28 coinduced by nicotine and either ethanol or heat.

Abstract

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.Stress responses in mammalian cells are characterized by two readily measured events. First, the protein synthesis pattern of the stressed cell is modified. The rates of synthesis of many normal cell proteins are reduced, while the synthesis of a specific set of proteins (and the relevant mRNAs) is either enhanced or induced de novo. These latter proteins are termed stress proteins and are of two types: proteins common to many stresses and proteins specific to the individual inducer (23). The second event is the development, in the surviving cells, of a transient resistance to the stressor; this is frequently accompanied by cross-resistance to other inducers (10, 13, 21). Many investigators have suggested that the stress proteins are responsible for this induced resistance, although direct proof is lacking (20,36).Among the inducers of stress responses are heat shock; exposure to aliphatic alcohols (including ethanol), metals such as cadmium, or sodium arsenite; and release of cells from hypoxia (23). A common feature of these treatments is protein damage. Indeed, several studies have shown that damaged proteins or the intracellular presence of proteins deemed "foreign" by the cell can lead to the induction of a response that is similar to that seen after heat shock (1, 14, 19). The heat shock response has been studied far more extensively than any other stress response. The reasons for this include the current interest in the use of hyperthermia in cancer therapy, the ease of induction of the resp...

Comparision of Pure Nicotine and Smokeless Tobacco Extract Induced Formation of 8-OH-dG

“…Alteration of heat shock protein production, inhibition of cell metabolism and proliferation and induction of nuclear aberrations are some of the common results of smokeless tobacco extract and nicotine administration (Hahn et al 1991;Doolittle et al 1995;Trivedi et al 1990;Tipton et al 1995;Konno et al 1991;Lee et al 1996.). In addition, it has been demonstrated that both nicotine and smokeless tobacco administration results in generation of reactive oxygen species during in vitro experimental systems (Ashakumary et al 1996;Bagchi et al 1995).…”

Comparison of Pure Nicotine- and Smokeless Tobacco Extract-Induced Toxicities and Oxidative Stress

“…Alteration of heat shock protein production Hahn et al 1991), inhibition of cell metabolism and proliferation (Konno et al 1991;Waggoner and Wang 1994), and induction of nuclear aberrations (Livingstone et al 1990;Doolittle et al 1995) are some of the common results of smokeless tobacco extract and nicotine administration. In addition, it has been demonstrated that both nicotine and smokeless tobacco administration result in generation of reactive oxygen species in in vitro experimental systems Wetscher et al 1995a).…”

Synergistic induction of the heat shock response in Escherichia coli by simultaneous treatment with chemical inducers

“…There are examples of such synergy in mammalian (6,8,(13)(14)(15), fungal (4), and amphibian (7) cells. In four cases, this synergy is at the level of mRNA synthesis (4,7,14,15), suggesting transcriptional control.…”