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Roles of metallothionein and zinc transporters in the homeostasis of histochemically reactive zinc in mice Hsi, Sharon Wei-Yu

Abstract

Zinc is an essential trace mineral required for the normal function of many zinc-containing binding proteins. There are two intracellular pools of zinc: the non-exchangeable pool of zinc and the labile intracellular pool of zinc (LIPZ). In animal tissues, LIPZ is known as histochemically reactive zinc. The abundance of LIPZ has been shown to be critical to cellular functions such as cell proliferation and apoptosis. However, the mechanisms involved in LIPZ regulation are not clear. Since both metallothionein (MT) and, to some degree, zinc transporters have been shown to play important roles in zinc homeostasis, we hypothesized that the abundance of histochemically reactive zinc in mice will be homeostatically regulated through the interplay between MT and zinc transporters. The objective was to investigate the role of MT and zinc transporters in the homeostatic regulation of histochemically reactive zinc^ in response to various zinc intakes in mice. Twenty-three-day old metallothionein knockout (MT-KO) and the control metallothionein-wild type (MT-WT) mice were fed low- (2 mg Zn/kg diet), adequate- (30 mg Zn/kg diet), or high-zinc (150 mg Zn/kg diet) diet. MT-WT mice were maintained on their assigned diet for 2, 4, 7, or 21 days, and MT-KO mice were maintained on their assigned diet for 4 days before the liver and small intestine were removed for analyses. In MT-WT mice, body weight gain and feed intake were unaffected by zinc intake, but bone zinc concentration was reduced at low-zinc intake and increased at high-zinc intake. High-zinc intake caused zinc toxicity in MT-KO mice. In MT-WT mice, MT concentrations reflected dietary zinc intake in both the liver and small intestine. The abundance of histochemically reactive zinc in small intestine, but not that in the liver, also reflected zinc intake. The abundance of small intestinal histochemically reactive zinc was higher in MT-WT mice than that in MT-KO mice at each dietary zinc intake. Zinc transporters mRNA levels were generally not affected by dietary zinc intakes in both MT-KO and MT-WT mice. Overall, the data suggested that MT, but not zinc transporters, plays a role in the homeostatic regulation of histochemically reactive zinc in mice.

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