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: 7341086
• 负责人: BETH Yvonne BESECKER
• 金额: $ 5.94万
• 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/7341086
• 关键词: Acute; Acute Lung Injury; Acute-Phase Reaction; Adult Respiratory Distress Syndrome; Apoptosis; Attention; Cell Death; Cell Line; Cell Survival; Cells; Cessation of life; Condition; Cytoprotection; Cytoprotective Agent; Disease susceptibility; DsRed; Epithelial; Epithelial Cells; Epithelium; Equilibrium; Event; Family; Gene Expression; Homeostasis; Homologous Gene; Human; Human Genome; Immune response; Infection; Inflammation; Inflammatory; Intervention; Laboratories; Lung; Mammalian Cell; Mediating; Movement; Mus; Play; Regulation; Role; Rupture; Site-Directed Mutagenesis; Small Interfering RNA; Stimulus; Stress; Testing; Transfection; Zinc; Zinc deficiency; cell growth; concept; cytokine; deprivation; disorder prevention; innovation; insight; member; mutant; prevent; protein expression; protein function; protein structure function; response; solute; uptake; zinc-binding protein

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.

锌对细胞至关重要。细胞内的锌受到严格调节，因为锌缺乏和过量可能是有害的。锌 转运蛋白控制锌的运动，在维持细胞凋亡、细胞间平衡方面发挥着至关重要的作用。 生长发育、疾病预防等。我们的初步研究结果表明，锌转运蛋白 SLC39A8 是一个关键的调节因子 人肺上皮中锌稳态的影响。我们建议调节锌转运蛋白的表达和 炎症应激期间的功能是将锌转运到细胞中并启动细胞保护以防止死亡- 诱导刺激。我们的具体假设是锌输入蛋白 SLC39A8 是负责 增加锌的摄取并激活肺上皮针对炎症应激的先天保护反应。 该提案的主要目标是 1) 比较正常和正常状态下天然 SLC39A8 介导的锌摄取 炎症状况并确定其对原代人肺分化培养物中细胞存活的贡献 上皮细胞，然后 2) 确定 SLC39A8 蛋白结构和与细胞锌摄取和细胞功能相关的功能 通过定点诱变在 BEAS2B 人肺上皮细胞系中存活。 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。