Cigarette smoke exposure is a major cause of chronic obstructive pulmonary disease. Cadmium is a leading toxic component of cigarette smoke. Cadmium and zinc are highly related metals. Whereas, zinc is an essential metal required for normal health, cadmium is highly toxic. Zrt- and Irt-like protein 8 (ZIP8) is an avid transporter of both zinc and cadmium into cells and is abundantly expressed in the lung of smokers compared to nonsmokers. Our objective was to determine whether disturbed zinc homeostasis through diet or the zinc transporter ZIP8 increase susceptibility to lung damage following prolonged cigarette smoke exposure.

Methods

Cigarette smoke exposure was evaluated in the lungs of mice subject to insufficient and sufficient zinc intakes, in transgenic ZIP8 overexpressing mice, and a novel myeloid-specific ZIP8 knockout strain.

Results

Moderate depletion of zinc intakes in adult mice resulted in a significant increase in lung cadmium burden and permanent lung tissue loss following prolonged smoke exposure. Overexpression of ZIP8 resulted in increased lung cadmium burden and more extensive lung damage, whereas cigarette smoke exposure in ZIP8 knockout mice resulted in increased lung tissue loss without a change in lung cadmium content, but a decrease in zinc.

Conclusions

Overall, findings were consistent with past human studies. Imbalance in Zn homeostasis increases susceptibility to permanent lung injury following prolonged cigarette smoke exposure. Based on animal studies, both increased and decreased ZIP8 expression enhanced irreversible tissue damage in response to prolonged tobacco smoke exposure. We believe these findings represent an important advancement in our understanding of how imbalance in zinc homeostasis and cadmium exposure via tobacco smoke may increase susceptibility to smoking-induced lung disease.

中文翻译：

---

锌稳态失衡会加剧香烟烟雾暴露后的肺组织损失

接触香烟烟雾是慢性阻塞性肺病的主要原因。镉是香烟烟雾中的主要有毒成分。镉和锌是高度相关的金属。锌是正常健康所需的必需金属，而镉则具有剧毒。Zrt 和 Irt 样蛋白 8 (ZIP8) 是将锌和镉转运到细胞中的快速转运蛋白，与不吸烟者相比，在吸烟者的肺部表达丰富。我们的目的是确定通过饮食或锌转运蛋白 ZIP8 扰乱锌稳态是否会增加长期接触香烟烟雾后肺损伤的易感性。

方法

在锌摄入不足和充足的小鼠、转基因 ZIP8 过表达小鼠以及新型骨髓特异性 ZIP8 敲除菌株的肺部中评估了香烟烟雾暴露情况。

结果

成年小鼠中度摄入锌会导致长期吸烟后肺镉负荷显着增加和永久性肺组织损失。ZIP8的过度表达导致肺镉负荷增加和更广泛的肺损伤，而ZIP8基因敲除小鼠的香烟烟雾暴露导致肺组织损失增加，肺镉含量没有变化，但锌含量减少。

结论

总体而言，研究结果与过去的人类研究一致。长期接触香烟烟雾后，锌稳态失衡会增加对永久性肺损伤的易感性。根据动物研究，ZIP8 表达的增加和减少都会增强因长期接触烟草烟雾而导致的不可逆组织损伤。我们相信，这些发现代表了我们对锌稳态不平衡和烟草烟雾中镉暴露如何增加对吸烟引起的肺部疾病的易感性的理解的重要进展。