Role of heat shock proteins in gastric mucosal protection

Heat shock proteins (HSP) are crucial for the maintenance of cellular homeo stasis during normal cell growth and for survival during and after various cellular stresses. Gastric surface mucous cells are the first line of defen ce against insults derived from ingested foods and Helicobacter pylori infe ction. Primary cultures of gastric surface mucous cells from guinea-pig fun dic glands exhibited a typical heat shock response after exposure to elevat ed temperature or metabolic insults, such as ethanol and hydrogen peroxide, and they were able to acquire resistance to these stressors. Restraint and water immersion stress rapidly activated heat shock factor 1 (HSF1) in rat gastric mucosa within IT min and induced HSP70 mRNA expression and its pro tein accumulation. The extent of the induction inversely correlated with th e severity of mucosal lesions, suggesting an important role of HSP70 in gas tric mucosal defence. This heat shock response appeared to be mediated by t he alpha(1A)-adrenoceptor. The HSP70 family functions as a molecular chaper one and reduces stress-induced denaturation and aggregation of intracellula r proteins. In addition to its chaperoning activities, HSP70 has been sugge sted to exert its cytoprotective action by protecting mitochondria and by i nterfering with the stress-induced apoptotic programme. Recently, we introd uced geranylgeranylacetone as a non-toxic HSP70 inducer. This compound weak ly stimulated HSP70 induction in cultured gastric mucosal cells and gastric mucosa by directly activating HSF1 and markedly augmented HSP70 induction in response to subsequent exposure to stress. Thus, non-toxic HSP70 inducer s may have a potential benefit for the prevention and treatment of stress u lcer. (C) 2000 Blackwell Science Asia Pty Ltd.