The heat-shock response in cultured cells exposed to ethanol and its metabolites.
Many stresses, including elevated temperature and exposure to toxins or heavy metals, activate a stereotyped response of cultured cells known as the heat-shock response. The products of several highly conserved heat-shock genes (heat-shock proteins) protect the cells against subsequent stresses. The intracellular signal for the response is unknown, but may include the presence of damaged and abnormal proteins in the cell. Ethanol at high concentration (1.3 mol/L) has been shown to activate the heat-shock response in hamster ovary fibroblasts, suggesting that this response might be an important consequence of exposure of cells to ethanol and might mediate some of its cellular toxicity. To determine if lower concentrations of ethanol or its metabolites could activate a heat-shock response, we transfected COS-1 cells with a reporter gene (the Drosophila 70 kd heat-shock protein promoter fused to the beta-galactosidase gene), then exposed them to various compounds. Exposure to heat induced at least a threefold to fourfold increase in beta-galactosidase activity, whereas 1.3 mol/L ethanol induced a sixfold increase. Lower concentrations of ethanol (100 to 500 mmol/L) or acetaldehyde (100 to 500 mumol/L) did not induce a measurable heat-shock response. Similarly, high concentrations of metabolites generated during ethanol oxidation (10 mmol/L lactate or acetate) did not induce the response. We conclude that the heat-shock response cannot be detected with this assay system in COS-1 cells after short exposure to physiologically achievable concentrations of ethanol or its metabolites. However, it is possible that it is induced at a low level or in tissues directly exposed to alcoholic beverages (e.g., oropharynx, esophagus, and stomach).
Walsh
K H
KH
Department of Medicine, Indiana University School of Medicine.
Crabb
D W
DW
D000079:Acetaldehyde / Q000494:pharmacology*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D000431:Ethanol / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids; D001616:beta-Galactosidase / Q000378:metabolism
D006360:Heat-Shock Proteins; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D001616:beta-Galactosidase; D000079:Acetaldehyde