Zinc Supplementation in a Randomized Controlled Trial Decreased<i>ZIP4</i>and<i>ZIP8</i>mRNA Abundance in Peripheral Blood Mononuclear Cells of Adult Women

Bogale, Alemtsehay; Clarke, Stephen; Fiddler, Joanna; Hambidge, K. Michael; Stoecker, Barbara J.

doi:10.4137/nmi.s23233

Cited by 13 publications

(9 citation statements)

References 52 publications

(78 reference statements)

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“…Here we confirmed ZIP4 overexpression in different ID8-P1 vs. ID8-P0 cells at the protein level (Figure 1A ). Previously ZIP4 regulation had been exclusively studied in the context of Zn [ 7 , 36 ]. The dramatic changes in ID8-P1 were only seen after cells were in vivo passaged, but not in vitro , strongly suggesting that the tumor microenvironment is important for these changes.…”

Section: Resultsmentioning

confidence: 99%

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The novel ZIP4 regulation and its role in ovarian cancer

Fan

Cai

et al. 2017

Oncotarget

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Our RNAseq analyses revealed that ZIP4 is a top gene up-regulated in more aggressive ovarian cancer cells. ZIP4's role in cancer stem cells has not been reported in any type of cancer. In addition, the role and regulation of ZIP4, a zinc transporter, have been studied in the context of extracellular zinc transporting. Factors other than zinc with ZIP4 regulatory effects are essentially unknown. ZIP4 expression and its regulation in epithelial ovarian cancer cells was assessed by immunoblotting, quantitative PCR, or immunohistochemistry staining in human ovarian tissues. Cancer stem cell-related activities were examined to evaluate the role of ZIP4 in human high-grade serous ovarian cancer cells in vitro and in vivo. RNAi and CRISPR techniques were used to knockdown or knockout ZIP4 and related genes. Ovarian cancer tissues overexpressed ZIP4 when compared with normal and benign tissues. ZIP4 knockout significantly reduced several cancer stem cell-related activities in EOC cells, including proliferation, anoikis-resistance, colony-formation, spheroid-formation, drug-resistance, and side-population in vitro. ZIP4-expressing side-population highly expressed known CSC markers ALDH1 and OCT4. ZIP4 knockout dramatically reduced tumorigenesis and ZIP4 overexpression increased tumorigenesis in vivo. In addition, the ZIP4-expressing side-population had the tumor initiating activity. Moreover, the oncolipid lysophosphatic acid effectively up-regulated ZIP4 expression via the nuclear receptor peroxisome proliferator-activated receptor gamma and lysophosphatic acid 's promoting effects in cancer stem cell-related activities in HGSOC cells was at least partially mediated by ZIP4 in an extracellular zinc-independent manner. Our critical data imply that ZIP4 is a new and important cancer stem cell regulator in ovarian cancer. Our data also provide an innovative interpretation for the apparent disconnection between low levels of zinc and up-regulation of ZIP4 in ovarian cancer tissues.

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Section: Resultsmentioning

confidence: 99%

“…The regulation and activities of ZIP4, an important Zn transporter, have been exclusively studied in the context of Zn [ 6 , 36 , 61 ]. The ZIP4 promoter has only been minimally studied in mouse brain tissue and mouse intestinal epithelial cells [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The novel ZIP4 regulation and its role in ovarian cancer

Fan

Cai

et al. 2017

Oncotarget

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“…Common reasons for exclusion included lack of intervention or baseline measurement or control group, pre-existing health condition (e.g., diabetes), <18 y of age, or the study exclusively used animals or commercialized cell lines. One study was not included because high-quality RNA was isolated from only 6-9 subjects despite samples having been obtained from 48 subjects (22). Sixteen studies were included in the qualitative synthesis.…”

Section: Resultsmentioning

confidence: 99%

Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review

Hennigar

Kelley

McClung

2016

Advances in Nutrition

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Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion. Cell types included leukocytes, peripheral blood mononuclear cells, T lymphocytes, monocytes, and erythrocytes. ZIP1, ZnT1, and metallothionein were the most commonly measured proteins. Changes in ZIP1 and ZnT1 in response to zinc supplementation or depletion were not consistent across studies. Leukocyte metallothionein decreased with zinc depletion (-39% change from baseline, <5 mg Zn/d, n = 2 studies) and increased with zinc supplementation in a dose-dependent manner (35%, 15-22 mg Zn/d, n = 7 studies; 267%, 50 mg Zn/d, n = 2 studies) and at the earliest time points measured; however, no change or delayed response was observed in metallothionein in erythrocytes. A greater percentage of studies demonstrated that metallothionein in leukocyte subtypes was a more reliable (100%, n = 12; 69%, n = 16) and responsive (92%, n = 12; 82%, n = 11) indicator of zinc exposure than was plasma zinc, respectively. In conclusion, current evidence indicates that metallothionein in leukocyte subtypes may be a component in determining zinc status.

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“…These supplementations are remarkably free of toxicity (18,41) and they been used as an available and inexpensive food condiment for human consumption. It is proposed that their usage may show synergistic effects in prediabetes.…”

Section: Curcumin Modulates the Several Cellular Transduction Pathwaymentioning

confidence: 99%

Evaluation of the Effect of Curcumin and Zinc Co-Supplementation on Glycemic Measurements, Lipid Profiles, Inflammatory and Antioxidant Biomarkers in Overweight or Obese Pre-Diabetic Patients: A study Protocol for a Randomized Double-Blind Placebo-Controlled Phase 2 Clinical Trial

Karandish

Mozaffari‐Khosravi

Mohammadi

et al. 2020

Preprint

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Background: The prevalence of prediabetes is increasing worldwide. Unfortunately, prediabetes is related to non-communicable diseases. A high risk of developing type 2 diabetes mellitus (T2DM) is reported in people with prediabetes. Curcumin, a polyphenol, might lead to its therapeutic role in obesity and some obesity-related metabolic diseases. Zinc is a trace element that plays a key role in the synthesis and action of insulin, carbohydrate metabolism, and decreasing inflammation. There has been no clinical trial of zinc and curcumin co-supplementation in patients with prediabetes. In previous studies, the single administration of zinc or curcumin hasn’t been conducted on many of the studied markers in pre-diabetic patients. Methods: The propose of this randomized double-blind placebo-controlled clinical trial is to investigate the effect of curcumin and zinc co-supplementation on glycemic measurements, lipid profiles, inflammatory and antioxidant biomarkers among 84 pre-diabetic patients with body mass index (BMI) between 25 and 35. Also, liver enzyme, serum zinc, urine zinc, blood pressure, anthropometric parameters, quality of life, adherence to co-supplementation, the side effects of co-supplementation, physical activity, and dietary intake will be assessed. Women or men (18-50 years old, for women: 18 years - before menopause) will be followed for three months (90 days). This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences. Discussion: A diet rich in antioxidants, polyphenols, and phytochemicals has been shown to have a beneficial role in prediabetes. According to the beneficial properties of curcumin or zinc and inadequate evidence, RCTs are needed to assess the effect of curcumin and zinc co-supplementation in native prediabetes patients. We hope the results of the present trial, negative or positive, fill this gap in the literature and facilitate the approach for a much larger, multi-center clinical trial. In conclusion, a synergic effect of co-supplementation along with a weight-loss diet may delay the progression to type 2 diabetes mellitus.Trial registration: The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.

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Zinc Supplementation in a Randomized Controlled Trial DecreasedZIP4andZIP8mRNA Abundance in Peripheral Blood Mononuclear Cells of Adult Women

Cited by 13 publications

References 52 publications

The novel ZIP4 regulation and its role in ovarian cancer

The novel ZIP4 regulation and its role in ovarian cancer

Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review

Evaluation of the Effect of Curcumin and Zinc Co-Supplementation on Glycemic Measurements, Lipid Profiles, Inflammatory and Antioxidant Biomarkers in Overweight or Obese Pre-Diabetic Patients: A study Protocol for a Randomized Double-Blind Placebo-Controlled Phase 2 Clinical Trial

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