& Hart, E. B. 1993, Oner et al. The pituitary contains a higher concentration of zinc than other organs, and zinc enhances pituitary hormone function (Henkin 1976). The reactive bands were visualized by chemiluminescence, and bands were quantified by densitometry. IGFBP-3 was determined in cell lysates by Western immunoblotting. Although zinc was first recognized as essential for growth in rats > 65 y ago (Todd et al. 1987, Clegg et al. The high concentrations of zinc in the pituitary, therefore, may provide for formation of dimerized GH, which is less susceptible to degradation. In this study, we show that exposure of cultured cortical neurons from mouse to increasing concentrations of Zn 2+ (10–300 μ m) induces a progressive decrease in global protein synthesis. Foods that don’t naturally contain this mineral, such as breakfast cereals, snack bars and baking flour, are often fortified with synthetic forms of zinc. In some studies, serum IGF-I levels in zinc-depleted and pair-fed rats were not different from each other but were lower compared with those of zinc-adequate ad libitum–fed rats (Bolze et al. In protein zinc-binding sites, the zinc ion is coordinated by different combinations of protein side chains, including the nitrogen of histidine, the oxygen of aspartate or glutamate and the sulfur of cysteine; among these, histidine is most commonly observed, followed by cysteine (Gregory et al. 1991), and zinc facilitates the binding of protein kinase C to the cytoskeleton (Forbes et al. Zinc contributes to the maintenance of normal hair, skin and nails. Furthermore, tibial zinc concentration, which is a sensitive measure of zinc status, was positively correlated with serum IGF-I concentration (Cossack 1984). The metallothionein transcriptional factor-1 binds to metal response elements and activates metallothionein gene expression. B3 cells were cultured in completed medium, followed by 2 d in medium with 2% serum. Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Zinc also influences hormonal regulation of cell division. The failure to correct growth with increased food intake suggests that growth is the first limiting role for zinc. Hence, zinc is required for some aspect of growth regulation at the cellular level that is independent of the effects observed on circulating IGF-I and GH. 1994). The protein kinase C signal transduction pathway may also regulate the transcription of metallothionein genes (Yu et al. 11). Hence, increased IGF binding protein-3 in cells incubated with DTPA would perhaps sequester IGF-I and render it unavailable to bind, and hence activate, the membrane receptor. Ruth S. MacDonald, The Role of Zinc in Growth and Cell Proliferation, The Journal of Nutrition, Volume 130, Issue 5, May 2000, Pages 1500S–1508S, https://doi.org/10.1093/jn/130.5.1500S. In humans, zinc deficiency decreased circulating IGF-I concentrations independently of total energy intake (Cossack 1991). Panel A: Cells were cultured in 2% serum for 2 d and then stimulated by growth factors, platelet-derived growth factor (P), epidermal growth factor (E) and insulin-like growth factor (I), with 600 μmol/L diethylenetriaminepentaacetic acid (DTPA). Zinc appears to regulate thymidine kinase mRNA through zinc-dependent protein binding to the promoter region of the gene (Chesters et al. Bunce (1994) recently reviewed the relationships among the clinical effects of zinc deficiency on embyrogenesis, growth and differentiation and regulation of the nuclear hormone receptor superfamily. Pituitary release of GH in response to GH-releasing factor was not different between zinc-adequate and deficient rats (Dorup et al. Zinc is required for numerous processes in your body, including (1): Zinc is naturally found in a wide variety of both plant and animal foods. Zinc contributes to normal cognitive function. 1993). The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases is activated in response to stress (Ip and Davis 1998). a * (Received for publication, May 20, 1999, and in revised form, August 6, 1999) Zinc is involved in many important processes in your body and absolutely essential for good health. Using Western immunoblotting, we found a significant increase in IGF binding protein-3 concentration in 3T3 cells incubated with DTPA compared with DTPA plus zinc or control cultures (Fig. After 11 d of feeding the deficient diet, less total DNA was present in liver and kidney compared with controls. To investigate the role of zinc in IGF-I regulation of cell division, we used the cell culture model developed and characterized by Chesters et al. Can You Use Zinc for Acne Spots and Scars? Research shows that zinc has numerous health benefits. Insulin-like growth factor-I levels in zinc-depleted rats not treated with IGF-I were significantly lower than those of any other treatment group. Growth is regulated hormonally by several systems, but the main influence on somatic growth is provided by growth hormone (GH)3 and insulin-like growth factor-I (IGF-I). However, force-feeding a zinc-depleted diet to rats failed to correct growth and exacerbated the clinical symptoms of the deficiency (Park et al. (, Prasad, A. S., Beck, F. W., Endre, L., Handschu, W., Kukuruga, M. & Kumar, G. (, Prasad, A. S., Oberleas, D., Wolf, P. & Horwitz, J. P. (, Rajaram, S., Baylink, D. J. Lack of an appropriate assessment tool makes it difficult to estimate deficiency prevalence, but undiagnosed marginal zinc deficiency may be a concern. However, maintaining serum IGF-I levels by exogenous administration or by inducing food intake (Browning et al. When the bone tissue from older rats were cultured with [3H]leucine, incorporation of … Glucocorticoid receptor-targeted liposomal delivery system for delivering small molecule ESC8 and anti-miR-Hsp90 gene construct to combat colon cancer. Insulin-like growth factor-I associates with IGF binding proteins in the circulation; at least eight distinct binding proteins have been identified thus far (Rajaram et al. 1993), the overall failure to stimulate growth may have been due to inadequate dietary intake. This article tells you all you need to know about…. Impaired mitogenic hormone signal transduction may also occur, resulting in depressed cell division. Additionally, in a large study in over 4,200 people, taking daily antioxidant supplements — vitamin E, vitamin C and beta-carotene — plus 80 mg of zinc decreased vision loss and significantly reduced the risk of advanced AMD (18). After 8 d, serum IGF-I levels were similar in the zinc-depleted rats treated with IGF-I and the zinc-adequate rats not treated with IGF-I. 3T3 cells, however, were not a useful model to study this phenomenon because of their low receptor number. 2). It may reduce inflammation and your risk of some age-related diseases. Metallothionein induction by zinc was inhibited in Chinese hamster ovary K1 cells by protein kinase C inhibitors. Keep in mind that zinc found in plant-based sources like legumes and whole grains is absorbed less efficiently because of other plant compounds that inhibit absorption (33). The decreased GH binding was associated with decreased serum IGF-I and hepatic IGF-I mRNA. Activation of the IGF-I receptor has been proposed to be the restriction point of the G1-to-S phase transition (Campisi and Pardee 1984). 8B), indicating IGF binding protein-3 sequestered IGF-I and reduced the IGF-I–IGF-I receptor interaction. The correctly folded proteins are synthesized by the … However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling. However, this does not apply to people with zinc deficiencies, who may need to take high-dose supplements. A potential chemical signal that responds to mitogenic hormone stimulation and induces transition of cells from G1 to S phase of the cell cycle is diadenosine tetraphosphate (Grummt et al. Using this model, we verified that DTPA inhibited thymidine uptake, and adding zinc with DTPA restored thymidine uptake to control levels (MacDonald et al. We used two techniques to maintain serum IGF-I concentrations in zinc-depleted rats (Browning et al. Despite the diversity of functions that zinc metalloenzymes affect, correlations between loss of enzyme activity and characteristics of zinc-deficiency have proved unsuccessful. (1989). Oxidative stress leads to chronic inflammation, a contributing factor in a wide array of chronic illnesses, such as heart disease, cancer and mental decline (24). Zinc deficiency in animals is characterized by growth inhibition and decreased food intake. Zinc contributes to normal protein synthesis Hyperoxia-induced miR-342-5p downregulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3. 1991), which indicated that the GH secretory pathway in the pituitary was functional in zinc-deficient rats. 1992), reverse transcriptases … Ingesting too much zinc can also cause deficiencies in other nutrients. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Zinc is essential for cell growth and division, immune function, enzyme reactions, DNA synthesis and protein production. (, Chesters, J. K., Petrie, L. & Vint, H. (, Clegg, M. S., Keen, C. L. & Donovan, S. M. (, Cunningham, B. C., Bass, S., Fuh, G. & Wells, J. We therefore concluded that IGF-I receptor activation, at the level of receptor and insulin response substrates-1/2 phosphorylation, was not affected by zinc depletion and therefore could not explain the growth inhibition. The increased IGF binding protein-3 may prevent IGF-I binding to the receptor and thereby prevent initiation of DNA synthesis. Zinc contributes to the normal function of the immune system. 1990). Our website services, content, and products are for informational purposes only. 1995). The binding of GH to the prolactin receptor, but not to the GH receptor, requires zinc (Cunningham et al. 1998). Panel B: Cumulative body weight gain on d 8. Zinc o Type of micronutrient essential mineral o Function Zinc plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. & LeRoith, D. (, Kirchgessner, M., Moser, C. & Roth, H. P. (, Kleppisch, T., Klinz, F. J. Decreased hepatic IGF-I release could therefore be explained by a defect in hepatic GH receptors or postreceptor signaling. Although this finding was consistent, the decrease in binding of cells was not sufficient to explain the inhibition of thymidine uptake observed in cells incubated with DTPA. 8A). Guest editors for this publication were Michael Hambidge, University of Colorado Health Science (Washington DC)s Center, Denver; Robert Cousins, University of Florida, Gainesville; Rebecca Costello, Office of Dietary Supplements, NIH, Bethesda, MD; and session chair, Craig McClain, University of Kentucky, Lexington. Protein Synthesis Zinc Top 15 Reasons to Avoid Low Carb Diets...When insulin ranges are chronically as well minimal as they may wellbe in incredibly minimal carb diet programs, catabolism (breakdown) ofmuscle mass protein increases, and protein synthesis stops. The binding of QM to c-Jun was also inhibited by phosphorylation of QM by protein kinase C. Hence, activation of protein kinase C, by IGF-I, for example, would result in reduced QM binding to c-Jun. Data are expressed as relative intensities. The potency of Zn 2+ was increased by about 2 orders of magnitude in the presence of Na + -pyrithione, a Zn 2+ ionophore. 1994). Growth occurs through cell division and requires DNA, RNA and protein synthesis. Acne is driven by obstruction of oil-producing glands, bacteria and inflammation (20). 1998). Zinc serves as a necessary structural component of DNA-binding proteins that affect gene expression. The GH administered to the zinc-depleted rats failed to increase circulating IGF-I concentrations (Dicks et al. Thymidine kinase is not a zinc metalloenzyme, but the transcription of the enzyme appears to be regulated by zinc availability. Zinc deficiency can and will result in a Force-feeding a zinc-depleted diet to rats for 14 d resulted in a 28% decrease in serum IGF-I compared with rats fed a zinc-adequate diet, although food intake was similar. Zinc is of particular interest to vegans and vegetarians since anti-nutrients like phytates limit the bioavailability and absorption of zinc from plant foods. The second technique used to maintain serum IGF-I levels during zinc depletion of rats was to administer megestrol acetate to induce food intake. Scientific Opinion on the substantiation of health claims related to zinc and maintenance of normal skin (ID 293), DNA synthesis and cell division (ID 293), contribution to normal protein synthesis (ID 293, 4293), maintenance of normal serum testosterone concentrations (ID 301), “normal growth” (ID 303), reduction of tiredness and fatigue (ID 304), … The most common cause of zinc toxicity is too much supplemental zinc, which can cause both acute and chronic symptoms. 1992), reverse transcriptases and transcription factor IIIA (Wu and Wu 1987). means that we need to obtain small amounts of it through our diet to remain healthy (, Wu, F. Y., Huang, W. J., Sinclair, R. B. Zinc is commonly used in hospitals as a treatment for burns, certain ulcers and other skin injuries (10). A. Body weight gain was significantly less after d 8 in rats fed the zinc-deficient compared with those fed the zinc-adequate diet, but the administration of IGF-I did not affect growth in either diet group (Fig. These herbs, vitamins, and natural supplements can be used to increase testosterone levels and help people coping with testosterone-related problems. 1984). Zinc toxicity may cause diarrhea, headache, abdominal cramps and reduced immunity. 1998). 1998). Health Benefits … Thymidine uptake (4 h) was determined and expressed as Bq incorporated/mg cell protein. & Bala, R. M. (, Park, J. H., Grandjean, C. J., Antonson, D. L. & Vanderhoof, J. After 8 d, serum IGF-I levels were similar in the zinc-depleted, megestrol acetate–treated rats compared with the zinc-adequate rats (Fig. 1998). The inhibition was reversed by adding zinc and iron, but not iron alone, with the chelator. Hence, in the absence of adequate zinc, serum IGF-I concentrations are not maintained even when energy intake is adequate. Reductions in copper levels have even been reported in people consuming only moderately high doses of zinc — 60 mg per day — for 10 weeks (36). Zinc Inhibits Protein Synthesis in Neurons. & Powers, L. (. (1969) administered bovine GH (40 μg/d) by subcutaneous injection for 2 wk to rats that had previously been fed a zinc-depleted diet for 3 wk and found no stimulation of growth compared with rats not fed GH. 3). Zinc deficiency had no apparent effect on liver weight, protein content, or RNA content when these properties were compared with values obtained using pair-fed rats. Thus, you may still be deficient even if tests indicate normal levels. 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