metallothionein and Deficiency-Diseases

The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases.

Topics: Aging; Apoptosis; Chronic Disease; Deficiency Diseases; Dietary Supplements; Homeostasis; Humans; Immunity; Metallothionein; Oxidative Stress; Trace Elements; Zinc; Zinc Compounds

In this paper, the progress on study of zinc deficiency and immunity including the relationship between zinc deficiency and the apoptosis of T cell, B cell, the expression of MT, immunological function of red cell, and non-specific immune system were reviewed.

Topics: Animals; Apoptosis; Deficiency Diseases; Erythrocytes; Immune System; Lymphocytes; Metallothionein; Mice; Rats; Zinc

The assessment of marginal zinc status is problematic. Currently, there is no universally accepted single measure to assess zinc status in humans. The development of a reliable measure of marginal or moderate zinc status would be useful for a variety of purposes. For example, a simple, yet sensitive and accurate measure of zinc nutritional status is critically needed to further our limited understanding of the possible associations between zinc status and the risk of developing various chronic diseases and in predicting favorable health outcomes in patient populations. A convenient and reliable zinc assessment tool is needed to identify subpopulations who are at a risk of zinc deficiency and as an objective guidepost to determine the need for initiation of zinc supplementation or zinc fortification of the food supply, as well in the refinement of recommendations of dietary zinc allowances. In frank zinc deficiency, clinical signs and static measures of zinc concentrations in a variety of readily available tissues, such as plasma, various blood cell types and hair, may uniformly confirm the presence of depleted body zinc stores. However, in general, the relative insensitivity or imprecision of these measurements has resulted in general disappointment in their use to assess marginal zinc status. Therefore, the search continues to find a useful and reliable marker of marginal zinc deficiency. In an attempt to speculate on possible future developments in the zinc status assessment field, a number of new and potentially promising approaches to this problem are highlighted.

Topics: Animals; Deficiency Diseases; Ferritins; Humans; Metallothionein; Nutrition Assessment; RNA, Messenger; Yeasts; Zinc

The absorption of zinc is increased when the dietary zinc supply is low. This is caused by increased intestinal transport and reduced secretion of endogenous zinc into the intestine. Kinetic analysis of zinc transport, based on data from either the isolated perfused intestine or brush border membrane vesicles, demonstrates uptake velocity is increased homeostatically by a carrier-mediated phase of transport in response to low dietary zinc. Zinc within intestinal cells binds to high molecular weight proteins and metallothionein. Expression of the metallothionein gene is altered by zinc status and the protein appears to have a function in intestinal cells. Zinc transport across the basolateral membrane is also carrier-mediated and may be ATP-driven. Newly absorbed zinc is transported via albumin, first to the liver and then is redistributed to other tissues, particularly muscle and bone which provide the greatest reserves. Plasma zinc levels remain relatively constant except during periods of dietary zinc depletion and acute responses to stress, infection or inflammation where they are depressed. Experiments with intact rats and isolated rat liver parenchymal cells have shown that hepatic zinc turnover is rapid. Stimulation of liver cells by glucocorticoids, glucagon, epinephrine, cAMP or interleukin-1-like factors alters uptake/exchange kinetics such that there is a net accumulation of cellular zinc. Metallothionein gene expression is enhanced by these hormonal signals, and a considerable portion of the newly accumulated zinc is accounted for as that associated with this zinc-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Biological Transport; Deficiency Diseases; DNA; DNA-Directed DNA Polymerase; Female; Humans; Infant; Intestinal Absorption; Liver; Metallothionein; Protein Binding; Rats; RNA; Tissue Distribution; Zinc

To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance.. Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of (55)Fe or (65)Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes.. Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were treated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.. Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.

Topics: Aconitate Hydratase; Animals; Animals, Newborn; Body Weight; Deficiency Diseases; Female; Glutathione Peroxidase; Intestinal Mucosa; Iron; Iron Deficiencies; Metallothionein; Oxidative Stress; Random Allocation; Rats; Rats, Inbred WKY; Superoxide Dismutase; Zinc