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Authors Walsh BM, Naik HB, Dubach JM, Beshire M, Wieland AM, Soybel DI
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Journal Am. J. Physiol., Cell Physiol. Volume: 293 Issue: 5 Pages: C1687-97
Publish Date 2007 Nov
PubMed ID 17287368

In Helicobacter pylori-induced gastritis, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the gastric mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NHCl), to serve as agonists of Ca(2+) accumulation within the parietal cell of the gastric gland. Individual gastric glands isolated from rabbit mucosa were loaded with fluorescent reporters for Ca(2+) in the cytoplasm (fura-2 AM) or intracellular stores (mag-fura-2 AM). Conditions were adjusted to screen out contributions from metal cations such as Zn(2+), for which these reporters have affinity. Exposure to NHCl (up to 200 microM) led to dose-dependent increases in intracellular Ca(2+) concentration ([Ca(2+)](i)), in the range of 200-400 nM above baseline levels. These alterations were prevented by pretreatment with the oxidant scavenger vitamin C or a thiol-reducing agent, dithiothreitol (DTT), which shields intracellular thiol groups from oxidation by chlorinated oxidants. Introduction of vitamin C during ongoing exposure to NHCl arrested but did not reverse accumulation of Ca(2+) in the cytoplasm. In contrast, introduction of DTT or N-acetylcysteine permitted arrest and partial reversal of the effects of NHCl. Accumulation of Ca(2+) in the cytoplasm induced by NHCl is due to release from intracellular stores, entry from the extracellular fluid, and impaired extrusion. Ca(2+)-handling proteins are susceptible to oxidation by chloramines, leading to sustained increases in [Ca(2+)](i). Under certain conditions, NHCl may act not as an irritant but as an agent that activates intracellular signaling pathways. Anti-NHCl strategies should take into account different effects of oxidant scavengers and thiol-reducing agents. Copyright © 2017 The Board of Regents of the University of Wisconsin System