Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.
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PMID:Synergism of Helicobacter pylori infection and stress on the augmentation of gastric mucosal damage and its prevention with alpha-tocopherol. 1589 Jun 19

With the discovery of gastric acid and pepsin in the stomach, the questions about "why does the stomach not digest itself?", "how does the stomach preserve its normal integrity under the continuous exposure to lytic materials that are secreted?", and "how does the stomach resist against overwhelming Helicobacter pylori (H. pylori) infection or persistent nonsteroidal anti-inflammatory drugs (NSAID) administration?" had been raised. The discovery of "gastric mucosal barrier" or "the presence of defense system" might be the answers to these questions. The first level of gastric mucosal barrier consists of the factors secreted into the lumen including bicarbonates, mucus, immunoglobulins, other antibacterial substances including lactoferrin, and surface active phospholipids. The second level of defense system is the gastric epithelia, which are remarkably resistant to acids or irritants and forms relatively tight barrier to passive diffusion. In addition, the epithelium is capable of undergoing extremely rapid repair and restitution if its continuity is disrupted. The third level of gastric mucosal barrier is the mucosal microcirculation in concert with sensory afferent nerves within the mucosa and submucosa. Back diffusion of acid or toxin into the mucosa results in neural system-mediated elevations of calcitonin gene related peptide, which contribute to enhancing mucosal blood flows that are very critical for limiting damage and facilitating repair. The fourth level of defense is the mucosal immune system, consisting of mast cells and macrophage, which orchestrate an appropriate inflammatory response to challenge. All the above factors are known to contribute to orchestrated artwork of "gastric mucosal protection". In recent years, heat shock proteins (HSPs) have been implicated to be an additional factor utilized for the gastric defense mechanisms at the intracellular level. Certain HSPs are expressed under non-stressful conditions and play an important role in the maintenance of normal cell integrity, but HSPs are generally considered to improve cellular recovery both by either refolding partially damaged functional proteins or increasing delivery of precursor proteins to important organelles such as mitochondria and endoplasmic reticulum, through which HSPs might complete efficient mucosal defense mechanisms and achieve ulcer healing, mostly probably protecting key enzymes related to cytoprotection. In this review, role of each heat shock protein, HSP90, HSP70, HSP27, in gastric inflammation and gastric ulcer healing will be described with general roles of HSPs.
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PMID:Role of heat shock proteins in gastric inflammation and ulcer healing. 2038 41