Monochloramine-induced toxicity and dysregulation of intracellular Zn 2+ in parietal cells of rabbit gastric glands

Jonathan E. Kohler, J. Matthew Dubach, Haley B. Naik, Kaniza Tai, Amy L. Blass, David Soybel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Monochloramine (NH2Cl) is a potent, thiol-directed oxidant capable of oxidizing thiol (S-H) residues in a wide variety of proteins. Generated in the stomach by the interaction of bacterial and host products, monochloramine has been shown to dysregulate Ca2+ homeostasis and disrupt mucosal integrity. In this report, we show that monochloramine also leads to disturbances in intracellular free zinc concentration ([Zn 2+]i) in the gastric gland of the rabbit and that the increased Zn2+ within the cell causes an independent decrease in cell viability. Changes in [Zn2+]i were measured by using the fluorescent reporter FluoZin-3, whereas cell viability was assessed by measuring the conversion of calcein-AM to fluorescent calcein, an assay that is not affected by intracellular oxidation state. Cell death was confirmed using propidium iodide and YO-PRO-1 dye uptake measurements. Our experiments demonstrate that [Zn2+]i is increased in gastric glands exposed to NH2Cl and that elevated [Zn2+]i decreases cell viability. Chelation of Zn2+ with tetrakis-(2- pyridylmethyl) ethylenediamine decreases the toxicity of NH2Cl, but only when administered concurrently. These findings suggest that the toxic effect of thiol oxidants present during chronic gastritis is partially due to dysregulation of [Zn2+]i early in the process and that zinc chelation can protect, but not rescue, gastric glands exposed to toxic doses of NH2Cl.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 1 2010

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Gastric Mucosa
Sulfhydryl Compounds
Cell Survival
ethylenediamine
Poisons
Rabbits
Oxidants
Zinc
Propidium
Gastritis
Stomach
Homeostasis
Cell Death
Coloring Agents
chloramine
Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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abstract = "Monochloramine (NH2Cl) is a potent, thiol-directed oxidant capable of oxidizing thiol (S-H) residues in a wide variety of proteins. Generated in the stomach by the interaction of bacterial and host products, monochloramine has been shown to dysregulate Ca2+ homeostasis and disrupt mucosal integrity. In this report, we show that monochloramine also leads to disturbances in intracellular free zinc concentration ([Zn 2+]i) in the gastric gland of the rabbit and that the increased Zn2+ within the cell causes an independent decrease in cell viability. Changes in [Zn2+]i were measured by using the fluorescent reporter FluoZin-3, whereas cell viability was assessed by measuring the conversion of calcein-AM to fluorescent calcein, an assay that is not affected by intracellular oxidation state. Cell death was confirmed using propidium iodide and YO-PRO-1 dye uptake measurements. Our experiments demonstrate that [Zn2+]i is increased in gastric glands exposed to NH2Cl and that elevated [Zn2+]i decreases cell viability. Chelation of Zn2+ with tetrakis-(2- pyridylmethyl) ethylenediamine decreases the toxicity of NH2Cl, but only when administered concurrently. These findings suggest that the toxic effect of thiol oxidants present during chronic gastritis is partially due to dysregulation of [Zn2+]i early in the process and that zinc chelation can protect, but not rescue, gastric glands exposed to toxic doses of NH2Cl.",
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Monochloramine-induced toxicity and dysregulation of intracellular Zn 2+ in parietal cells of rabbit gastric glands. / Kohler, Jonathan E.; Dubach, J. Matthew; Naik, Haley B.; Tai, Kaniza; Blass, Amy L.; Soybel, David.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 299, No. 1, 01.07.2010.

Research output: Contribution to journalArticle

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T1 - Monochloramine-induced toxicity and dysregulation of intracellular Zn 2+ in parietal cells of rabbit gastric glands

AU - Kohler, Jonathan E.

AU - Dubach, J. Matthew

AU - Naik, Haley B.

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AU - Soybel, David

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