Alcohol & FAS-Mediated Apoptosis in Polarized Liver Cell

酒精

• 批准号: 7564111
• 负责人: BENITA L. MCVICKER
• 金额: $ 11.15万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7564111
• 关键词: Activation Analysis; Alcohols; Apoptosis; Apoptotic; Architecture; Area; B-Lymphocytes; Biological Assay; Biological Models; CD95 Antigens; Cell Death; Cell Line; Cell membrane; Cell model; Cell physiology; Cell surface; Cells; Cessation of life; Characteristics; Consultations; District of Columbia; Doctor of Philosophy; Dose; Ethanol; Evaluation; Event; Fibroblasts; Flow Cytometry; Future; Gene Expression; Generations; Goals; Grant; Hepatocyte; Hybrid Cells; Instruction; Knowledge; Laboratories; Lead; Ligands; Liver; Location; Mediating; Medical center; Membrane; Mentors; Methods; Microinjections; Modeling; Nebraska; Pathway interactions; Phenotype; Phosphorylation; Play; Primary carcinoma of the liver cells; Property; Proteins; Receptor Signaling; Research; Role; Signal Transduction; Study models; System; TNFRSF6 gene; Techniques; Time; Trace Elements; Training; Training Support; Universities; Vesicle; Work; Zinc; alcohol abuse therapy; alcohol effect; bile canaliculus structure; cell injury; chronic alcohol ingestion; design; experience; functional mimics; in vivo; inhibitor/antagonist; interest; liver function; protein transport; receptor; research study; tool; trafficking

Benita L. McVicker received her PhD from The University of Nebraska Medical Center (UNMC) in 1997 and has worked in the laboratories of Drs. Dean Tuma and Carol Casey in the Liver Study Unit at the VA Medical Center in Omaha, Nebraska since that time. The Liver Study Unit has been instrumental in establishing that chronic ethanol consumption can lead to a variety of pathological consequences, yet further clarification of the mechanism(s) by which ethanol causes hepatotoxic conditions is required. Recently, Dr. McVicker and co-workers have identified the use of a fibroblast/hepatoma hybrid cell line (WIF-B) as a model for studying the effects of ethanol on cellular processes. The generation of such a physiologically important polarized model (that cannot be accomplished with regular isolated hepatocytes) will enable the evaluation of protein trafficking events (Fas/CD95 death receptor) in the presence of alcohol in relation to alterations in hepatocyte polarity and apoptosis. Specifically, the goals of Dr. McVicker's research presented in this grant include 1) further characterization of ethanol's effects on Fas trafficking and 2) to identify the role of specific regulators that are involved in ethanol-induced Fas translocation and the correlation of these effects with Fas-induced apoptosis mechanisms. The study of death receptor trafficking and signaling as well as the use of the WIF-B model are new areas of interest to Dr. McVicker. For these studies, she has proposed to use several techniques (i.e.immunohistochemistry and microinjection assays) that will require additional training and specialized instruction. Dr. McVicker has access to the confocal and flow cytometry core labs at UNMC and has support for training consultations in those methods. In addition, she has support to leam specific techniques under the direction of Dr. Pamela Tuma (an expert in the use of WIF-B cells) at The Catholic University in Washington D.C. Overall, the completion of this proposed work will provide the mentored experience to progress to future independent study of liver function and survival following ethanol treatment.

Benita L. McVicker 于 1997 年在内布拉斯加大学医学中心 (UNMC) 获得博士学位， 曾在博士的实验室工作。 Dean Tuma 和 Carol Casey 在 VA Medical 肝脏研究室 从那时起，中心就在内布拉斯加州奥马哈市。肝脏研究单位在确定这一点方面发挥了重要作用 长期摄入乙醇可导致多种病理后果，尚需进一步阐明 需要了解乙醇引起肝毒性病症的机制。最近，麦克维克博士和 同事们已经确定使用成纤维细胞/肝癌杂交细胞系（WIF-B）作为研究模型 乙醇对细胞过程的影响。这种生理上重要的极化的产生 模型（无法用常规分离的肝细胞完成）将能够评估蛋白质 酒精存在下的贩运事件（Fas/CD95 死亡受体）与 肝细胞极性和凋亡。具体来说，麦克维克博士在这笔赠款中提出的研究目标 包括 1) 进一步表征乙醇对 Fas 运输的影响，以及 2) 确定特定的作用 参与乙醇诱导的 Fas 易位的调节因子以及这些效应与 Fas 诱导的细胞凋亡机制。死亡受体运输和信号转导及其应用的研究 WIF-B 模型的研究是 McVicker 博士感兴趣的新领域。对于这些研究，她建议使用 需要额外培训的几种技术（即免疫组织化学和显微注射测定） 和专门指导。 McVicker 博士可以进入 UNMC 的共聚焦和流式细胞术核心实验室 并支持这些方法的培训咨询。此外，她还获得学习特定知识的支持 在天主教的 Pamela Tuma 博士（WIF-B 细胞使用专家）的指导下进行技术 华盛顿特区大学总体而言，完成这项拟议工作将提供指导 积累经验，以进一步开展乙醇治疗后肝功能和生存的独立研究。