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The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)–prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E2 (PGE2), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX–PG and free radicals, probably mediated by the changes in local gastric melatonin. [ABSTRACT FROM AUTHOR]

Background: The members of the family of heat shock factors coordinate the inducible transcription of heat shock genes in response to diverse stimuli. Any disturbances in signal transduction may lead to the attenuation of heat shock proteins synthesis and to cell death due to apoptosis. It has been shown by others that different nuclear factors, such as nuclear factor interleukine 6 or signal transducer and activator of transcription 3, co-operate with heat shock factors, mostly enhancing their activator effect on heat shock proteins genes expression. Therefore, we sought to determine whether apoptosis induced in the gastric epithelium exposed to live Helicobacter pylori might occur due to the elimination of HSP70 expression and deregulation of the heat shock response of the cell. Materials and Methods: Experiments were performed on KATO III gastric epithelial cells exposed to live cagA, vacA expressing Hp over different periods of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for polimerase chain reaction, western-blot, electrophoretic mobility shift assay, decoy and co-immunoprecipitation studies. Results: We found that in human gastric epithelium exposed to Helicobacter pylori, heat shock factor 1 is bound and restrained in complexes by phosphorylated signal transducer and activator of transcription 3 protein. In consequence, heat shock factor 1 bound up with phosphorylated signal transducer and activator of transcription 3 protein is unable to activate HSP70 protein synthesis in KATO III cells under stress conditions. Helicobacter pylori also causes changes in bax/bcl-2 cellular equilibrium, leading to the induction of apoptosis. Conclusions: The observed phenomenon might be the mechanism whereby gastric epithelium adapts to the infection of Helicobacter pylori, eliminating cells which are damaged or altered by bacterial cytotoxic products from the tissue. [ABSTRACT FROM AUTHOR]