In the present research, the effects of exposure to a sublethal concentration of zinc (Zn) on metal and ion homeostasis, and the regulation and the localization of various Zn transporters (i.e., the Zrt-Irt Like Protein (ZIP) family of Zn transporters), were investigated in zebrafish (Danio rerio) during early development. Exposure to an elevated level of Zn [4 μM (high) vs. 0.25 μM (control)] from 0 day post-fertilization (dpf) resulted in a significant increase in the whole body content of Zn at 5 dpf. A transient decrease in the whole body calcium (Ca) level was observed in 3 dpf larvae exposed to high Zn. Similarly, whole body nickel (Ni) and copper (Cu) contents were also reduced in 3 dpf larvae exposed to high Zn. Importantly, the magnitude of reduction in whole body Ni and Cu contents following Zn exposure was markedly higher than that in Ca content, suggesting that internal Ni and Cu balance were likely more sensitive to Zn exposure in developing zebrafish. Exposure to high Zn altered the mRNA expression levels of specific zip transporters, with an increase in zip1 (at 3 dpf) and zip8 (at 5 dpf), and a decrease in zip4 (at 5 dpf). The expression levels of most zip transporters tended to decrease from 3 dpf to 5 dpf with the exception of zip4 and zip8. Results from in situ hybridization revealed that several zip transporters exhibited distinct spatial distribution (e.g., zip8 in the intestinal tract, zip14 in the pronephric tubules). Overall, our findings suggested that exposure to sublethal concentrations of Zn disrupts the homeostasis of essential metals during early development and that different ZIP transporters may play unique roles in regulating Zn homeostasis in various organs in developing zebrafish.

在本研究中，暴露于亚致死浓度的锌（Zn）对金属和离子稳态的影响，以及各种锌转运蛋白（即锌转运蛋白的Zrt-Irt样蛋白（ZIP）家族）的调控和定位），在斑马鱼（Danio rerio）。受精后0天（dpf）暴露于升高水平的锌[4μM（高）相对于0.25μM（对照）]导致5dpf时锌的体内含量显着增加。在暴露于高锌的3 dpf幼虫中，观察到全身钙（Ca）含量短暂下降。同样，在暴露于高锌的3 dpf幼虫中，体内镍（Ni）和铜（Cu）的含量也降低了。重要的是，锌暴露后，体内镍和铜含量的降低幅度明显高于钙含量，这表明在发育中的斑马鱼内部，镍和铜的平衡可能对锌暴露更敏感。暴露于高锌会改变特定拉链转运蛋白的mRNA表达水平，并增加zip1（3 dpf）和zip8（5 dpf），而zip4（5 dpf）减少。除zip4和zip8以外，大多数zip转运蛋白的表达水平均从3 dpf降至5 dpf 。原位杂交的结果表明，几个拉链转运蛋白表现出明显的空间分布（例如，肠道中的zip8，zip14在肾小管中）。总体而言，我们的发现表明，在发育初期，暴露于亚致死浓度的Zn会破坏必需金属的稳态，而不同的ZIP转运蛋白可能在调节斑马鱼中各个器官的Zn稳态中起独特作用。