Zinc Importer SLC39A8 and Lung Epithelial Cell Survival

锌输入蛋白 SLC39A8 和肺上皮细胞存活

• 批准号: 7157330
• 负责人: BETH Yvonne BESECKER
• 金额: $ 5.74万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-08 至 2009-01-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157330
• 关键词: adult respiratory distress syndrome; apoptosis; cell line; clinical research; cytoprotection; gene expression; human tissue; inflammation; lung; membrane transport proteins; metal metabolism; postdoctoral investigator; protein localization; protein structure function; respiratory epithelium; site directed mutagenesis; tissue /cell culture; zinc

DESCRIPTION (provided by applicant): 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-inducing 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.

描述（由申请人提供）：锌对细胞至关重要。细胞内锌是严格调节的锌缺乏和过量可能是有害的。锌转运蛋白控制锌的运动，并在维持细胞凋亡、细胞生长和疾病预防之间的细胞平衡中起关键作用。我们的初步研究结果表明，锌转运蛋白，SLC39A8，是一个关键的调节人肺上皮锌稳态。我们提出，在炎症应激过程中，锌转运蛋白的表达和功能的调节是锌转运进入细胞所必需的，并启动细胞对死亡诱导刺激的保护。我们的具体假设是，锌输入SLC39A8是主要的转运蛋白，负责增加锌的吸收和激活先天性保护反应，对炎症应激的肺上皮细胞。该提议的主要目的是1）比较正常和炎症条件下天然SLC 39A8介导的锌摄取，并确定其对原代人肺上皮细胞分化培养物中细胞存活的贡献，然后2）通过定点诱变确定关于BEAS 2B人肺上皮细胞系中细胞锌摄取和细胞存活的SLC 39A8蛋白结构和功能。我们期望我们的研究结果将为ARDS疾病的易感性和治疗提供新的见解。