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

Abstract

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.

Expression of Metallothionein after Administration of Aspirin, Vitamin C or Zinc Supplement in the DMH Induced Colon Carcinoma in Rat

“…In the present study, it was observed that DMH treated rats supplemented with zinc from the initiation stage resulted in a significant increase in colonic MT mRNA in both precancerous and cancerous groups (3.6 fold and 33 fold respectively), which was reflected in the simultaneous increase in the immunohistochemical localisation of the MT protein (290%, cancer group) along with a concomitant raise in MT protein content (143%, cancer group) as compared with the DMH test group. Our results are in agreement with other studies that zinc supplementation has an effect on MT concentration and its mRNA synthesis in various tissues of growing rats, including esophagus and intestine (Liu et al, 2005) and in human Leukocytes (Hennigar, et al, 2016). These studies demonstrate the responsiveness of MT expression to zinc consumption in humans and rats and are enhanced by observations that zinc increases the susceptibility of cells to apoptosis (Kocdor et al, 2015).…”

Drosophila-associated bacteria differentially shape the nutritional requirements of their host during juvenile growth

“…Metallothioneins are intracellular proteins that can store Zn. Their expression, as well as expression of Zn transporters such as zip-3, is regulated by intracellular levels of Zn [87]. Altogether, these results suggest that host-associated bacteria may play an important role in the uptake of metals (especially Zn) by Drosophila larvae.…”

Interrelationships among mediators of cellular zinc homeostasis in healthy and type 2 diabetes mellitus populations

“…In the T2DM cohort, serum tubes were used for (3 of 9) 1600838 glucose and insulin analyses, and EDTA tubes for analysis of HbA1c. Details on blood collection and biochemical analyses were described previously [9][10][11]16].…”