Background: Myocardial ischemia-reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia-reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocyte damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Observations: An increase in the formation of reactive oxygen species during ischemia-reperfusion and the adverse effects of oxyradicals on myocardium have now been well established by both direct and indirect measurements. Although several experimental studies as well as clinical trials have demonstrated the cardioprotective effects of antioxidants, some studies have failed to substantiate the results. Nonetheless, it is becoming evident that some of the endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and catalase act as a primary defense mechanism whereas the others including vitamin E may play a secondary role for attenuating the ischemia-reperfusion injury. The importance of various endogenous antioxidants in suppressing oxidative stress is evident from the depression in their activities and the inhibition of cardiac alterations which they produce during ischemia-reperfusion injury. The effects of an antioxidant thiol containing compound, N-acetylcysteine, and ischemic preconditioning were shown to be similar in preventing changes in the ischemic-reperfused hearts. Conclusions: The available evidence support the role of oxidative stress in ischemia-reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.

Helicobacter pylori persistently colonize the human stomach and have been linked to atrophic gastritis and gastric carcinoma. Although it is well known that H. pylori infection can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood. Here we show that VacA permeabilizes the apical membrane of gastric parietal cells and induces hypochlorhydria. The functional consequences of VacA infection on parietal cell physiology were studied using freshly isolated rabbit gastric glands and cultured pari- Helicobacter pylori are Gram-negative bacteria that colonize the gastric mucosa in more than half of the world's human population and persist despite a vigorous host immune response. Infection with these organisms consistently results in gastric inflammation and is a risk factor for the development of peptic ulcer disease, distal gastric adenocarcinoma, and gastric lymphoma (1, 2). Some individuals who are persistently infected with H. pylori develop a body-predominant atrophic gastritis and profound suppression of gastric acid secretion (3, 4). Atrophic gastritis is considered a risk factor for the development of gastric adenocarcinoma (5). In addition to causing hypochlorhydria in the setting of chronic infection, H. pylori also can cause hypochlorhydria in the setting of acute infection (6). The molecular mechanisms underlying H. pylori-induced hypochlorhydria have remained incompletely understood.Acid secretion by the gastric parietal cell is regulated by paracrine, endocrine, and neural pathways. The physiological stimuli for acid secretion include histamine, acetylcholine, and gastrin, each of which binds to receptors located on the basolateral plasma membranes. Stimulation of acid secretion typically involves an activation of a cAMP-dependent protein kinase cascade that triggers the translocation and insertion of the proton pump enzyme, H,K-ATPase, into the apical plasma membrane of parietal cells (7). Ezrin is an actin-binding protein of the ezrin/radixin/moesin family of cytoskeleton-membrane linker proteins (8, 9) and, within the gastric epithelium, has been localized exclusively to parietal cells and primarily to the apical canalicular membrane of these cells (10). Our previous studies show that gastric ezrin is co-distributed with the ␤-actin isoform in vivo (11) and preferentially binds to the ␤-actin isoform in vitro (9). Based on the cytolocalization and observed stimulation-dependent phosphorylation of ezrin, it was postulated that ezrin couples the activation of protein kinase A to the apical membrane remodeling associated with parietal cell secretion (10, 12). Indeed, we have recently mapped the protein kinase A phosphorylation site on ezrin and elucidated the phosphoregulation of gastric acid secretion (13).

The aim of this study was to assess whether depression of cardiac Na+,K(+)-ATPase activity during ischemia/reperfusion (I/R) is associated with alterations in Na+,K(+)-ATPase isoforms, and if oxidative stress participates in these I/R-induced changes. Na+,K(+)-ATPase alpha1, alpha2, alpha3, beta1, beta2, and beta3 isoform contents were measured in isolated rat hearts subjected to I/R (30 min of global ischemia followed by 60 min of reperfusion) in the presence or absence of superoxide dismutase plus catalase (SOD+CAT). Effects of oxidative stress on Na+,K(+)-ATPase isoforms were also examined by perfusing the hearts for 20 min with 300 microM hydrogen peroxide or 2 mM xanthine plus 0.03 U/ml xanthine oxidase (XXO). I/R significantly reduced the protein levels of all alpha and beta isoforms. Treatment of I/R hearts with SOD+CAT preserved the levels of alpha2, alpha3, beta1, beta2, and beta3 isoforms, but not that of the alpha1 isoform. Perfusion of hearts with hydrogen peroxide and XXO depressed all Na+,K(+)-ATPase alpha and beta isoforms, except for alpha1. These results indicate that the I/R-induced decrease in Na+,K(+)-ATPase may be due to changes in Na+,K(+)-ATPase isoform expression and that oxidative stress plays a role in this alteration. Antioxidant treatment attenuated the I/R-induced changes in expression of all isoforms except alpha1, which appears to be more resistant to oxidative stress.