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Nutrient-Gene Interactions

The Permissive Effect of Zinc Deficiency on Uroguanylin and Inducible Nitric Oxide Synthase Gene Upregulation in Rat Intestine Induced by Interleukin 1 Is Rapidly Reversed by Zinc Repletion^1,2

Food Science and Human Nutrition Department and Center for Nutritional Sciences, University of Florida, Gainesville, FL 32611-0370

⁴To whom correspondence should be addressed. E-mail: cousins{at}ufl.edu.

Deficient intake of zinc from the diet upregulates both uroguanylin (UG) and inducible nitric oxide synthase (iNOS) expression in rats. Because these changes influence intestinal fluid secretion and intestinal cell pathophysiology, they relate to the incidence of diarrheal disease and its reversal by zinc as well as intestinal inflammation in general. A model of moderate zinc deficiency in rats, which changes molecular indices of zinc deficiency, was used to further explore the effects of the proinflammatory cytokine interleukin (IL)-1 and zinc repletion on these changes. IL-1 has been shown to have a role in the intestinal inflammation that occurs with bacterial infection. Our results showed a permissive effect of zinc deficiency on both UG and iNOS expression. Specifically, UG expression was responsive to zinc deficiency and IL-1 challenge, which were additive when combined, whereas iNOS expression was upregulated by IL-1 only during the deficiency. Immunohistochemistry showed that the increase in UG was limited to enterocytes of the upper villus but, in contrast, the increase in iNOS was principally in cells of the lamina propria of IL-1–treated rats. Cells exhibiting UG upregulation did not co-express serotonin. Repletion with zinc reversed upregulation of the iNOS gene within 1 d, whereas UG upregulation required 3–4 d to return to normal. This differential response to repletion suggests that mechanisms of UG and iNOS dysregulation are different. Dysregulation of both genes may contribute to the severity of zinc-responsive diarrheal disease and intestinal inflammatory disease.

KEY WORDS: • zinc deficiency • diarrheal disease • interleukin 1 • inflammation • gene regulation • rats

This article has been cited by other articles:

				R. J. Cousins, J. P. Liuzzi, and L. A. Lichten Mammalian Zinc Transport, Trafficking, and Signals J. Biol. Chem., August 25, 2006; 281(34): 24085 - 24089. [Full Text] [PDF]