28.9: Metallothionein mRNA expression in circulating blood cell types (24c.9)
- Page ID
- 117299
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Expression of the metallothionein gene is induced by zinc through the binding of zinc to metal-binding-regulatory transcription factor 1 (MTF-1). This transcription factor is known to be sensitive to cellular zinc concentrations, with metallothionein synthesis increasing as cellular zinc increases. Reverse transcriptase (RT) polymerase chain reaction (PCR) assays can be used to measure the response of metallothionein expression in various blood cell types to changes in dietary zinc. Hennigar et al. (2016), conducted a systematic review of sixteen experimentally controlled studies to determine the reliability and sensitivity of metallothionein expression to changes in dietary zinc in a variety of blood cell types. The studies were classified into three groups depending on the amount of zinc consumed per day (< 5, 15–22, and 50mg Zn/d). Only studies on healthy adults (> 18y) with no pre-existing health conditions, and that included baseline measurements or a placebo, were included. In all the studies, a depletion phase (mostly about 10 days) followed by repletion or a supplementation phase (ranging from 10 to 84 days) were included, although some also had a post-supplementation phase during which participants received a placebo tablet. Figure 24c.8
Figure 24c.8 Metallothionein expression in leukocytes. Values are percentage changes from baseline±SEs for all studies that examined metallothionein expression in leukocytes. In studies that determined metallothionein expression at multiple time points(19–21), the day with the greatest percentage change was used. Data are grouped based on the amount of dietary zinc consumed per day. From Hennigar et.al. (2016).
presents the estimated effect of varying concentrations of supplemental zinc on metallothionein expression in leukocytes based on the percentage change from baseline. There was a 39% decrease from baseline in metallothionein expression in leukocytes in participants consuming < 5mg Zn/d, and increases from baseline of 135% and 267% for those receiving 15–22mg Zn/d and 50mg Zn/d, respectively. Hence these findings indicate that metallothionein expression in leukocytes is sensitive to changes in dietary zinc intake, decreasing in zinc depletion, and increasing in response to zinc supplementation in a dose-dependent manner. However, these changes were not associated with consistent changes in plasma zinc, which suggests that metallothionein expression in leukocytes may be a more sensitive biomarker than plasma zinc for determining zinc exposure. Of interest was the lack of sensitivity of metallothionein expression in erythrocytes to changes in dietary zinc.
Clearly, further work is needed to investigate whether metallothionein expression in leukocytes can be used as a biomarker of zinc status among other age groups and free-living volunteers. The effect of potential confounders (e.g., inflammatory agents, free radicals, glucocorticoids, and pharmacologic agents)needs to be explored. In addition, more research is needed on whether the sensitivity to zinc supplementation and depletion is affected by variations in the proportions of blood cell subtypes among individuals. The abundance of metallothionein transcript in monocytes is three times that of granulocytes, and twice that found in T lymphocytes (Aydemir et al., 2006). In view of these uncertainties, metallothionein expression in various blood cell types was classified as an “emerging biomarker” by the BOND Zinc Expert Panel (King et al., 2015).