Abstract
Essential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, storage, and secretion. Some metal ions can be transformed by processes including reduction/oxidation (redox) reactions, and correspondingly, the breakdown of metal ion homeostasis can lead to formation of reactive oxygen and nitrogen species. We have previously demonstrated rapid biochemical responses to stress involving alterations in the redox state to generate free radicals and the resultant oxidative stress. However, the effects of stress on redox-active metals including iron and copper and redox-inert zinc have not been well characterised. Therefore, this study aims to examine the changes in these essential metals following exposure to short-term repeated stress, and to further elucidate the alterations in metal homeostasis through expression analysis of different metal transporters. Outbred male Wistar rats were exposed to unrestrained (control), 1 day, or 3 days of 6 h restraint stress (n = 8 per group). After the respective stress treatment, blood and liver samples were collected for the analysis of biometal concentrations and relative gene expression of metal transporter and binding proteins. Exposure to repeated restraint stress was highly effective in causing hepatic redox imbalance. Stress was also shown to induce hepatic metal redistribution, while modulating the mRNA levels of key metal transporters. Overall, this study is the first to characterise the gene expression profile of metal homeostasis following stress and provide insight into the changes occurring prior to the onset of chronic stress conditions.
Highlights
Transition metals including copper, iron, and zinc are key components for a variety of biological systems
Since the regulation of essential trace metals are tightly interlinked, this study aims to examine the changes in the three key essential metals, including copper, iron, and zinc, following exposure to short-term repeated stress, and to further elucidate the alterations in metal homeostasis through expression analysis of different metal transporters
As Cp is synthesised in the liver, where it incorporates six copper atoms and is secreted into the circulation, we looked at the mRNA expression of hepatic Cp
Summary
Transition metals including copper, iron, and zinc are key components for a variety of biological systems. Several of these essential trace metals are known to be redox-active, including copper and iron, making them catalytically active as cofactors in many metalloenzymes [1,2]. While zinc does not directly participate in redox reactions, it has the ability to modulate bound thiol groups in addition to acting as a stable biological cofactor required for the activity of more than 300 enzymes [3,4]. The metabolism and intracellular concentration of these metal ions is strictly regulated by metal transporters which mediate the import, distribution, and export from the cells to ensure normal enzymatic activity. Copper transfer is facilitated by specific copper chaperones such
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