Zinc Importer SLC39A8 and Lung Epithelial Cell Survival

锌是细胞所必需的。细胞内的锌受到严格的调控，因为缺锌和过量锌可能是有害的。锌 转运体控制着锌的运动，在维持细胞间的平衡中起着至关重要的作用 生长和疾病预防。我们的初步发现表明，锌转运蛋白SLC39A8是一个关键的调节因子 人体肺上皮中锌的动态平衡。我们认为锌转运蛋白的表达调控和 炎症应激时的功能是锌转运到细胞内所必需的，并启动细胞保护免受死亡- 产生刺激。我们的具体假设是，锌进口商SLC39A8是负责 肺上皮细胞锌摄取增加和对炎症应激的天然保护性反应的激活。 这项建议的主要目的是：1)比较天然SLC39A8介导的锌吸收在正常和 原代人肺分化培养中炎性条件及其对细胞存活的影响 然后测定SLC39A8蛋白的结构和功能与细胞锌摄取和细胞 定点突变在人肺上皮细胞系BEAS2B中的存活。 我们预计，我们的结果将为ARDS疾病的易感性和治疗提供新的见解。

Zinc is essential to cells. Intracellular zinc is tightly regulated as zinc deficiency and excess can be detrimental. Zinc transporters control movement of zinc and have a crucial role in maintaining cellular balance between apoptosis, cell growth, and disease prevention. Our preliminary findings indicate that the zinc transporter, SLC39A8, is a key regulator of zinc homeostasis in the human lung epithelium. We propose that modulation of zinc transporter expression and function during inflammatory stress is required for zinc transport into the cell and initiates cell protection against death- nducing stimuli. Our specific hypothesis is that the zinc importer SLC39A8 is the primary transporter responsible for increased zinc uptake and activation of an innate protective response against inflammatory stress in the lung epithelium. The key aims of this proposal are 1) To compare native SLC39A8-mediated zinc uptake during normal and inflammatory conditions and determine its contribution to cell survival in differentiated cultures of primary human lung epithelia and then 2) determine SLC39A8 protein structure and function with respect to cellular zinc uptake and cell survival in the BEAS2B human lung epithelial cell line via site-directed mutagenesis. We anticipate that our results will provide new insight into ARDS disease susceptibility and treatment.