ENDOTHELIAL CELL HYPOXIA ASSOCIATED PROTEINS

内皮细胞缺氧相关蛋白

• 批准号: 2028565
• 负责人: HARRISON W FARBER
• 金额: $ 32.28万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2028565
• 关键词: DNA footprinting; antisense nucleic acid; gel mobility shift assay; gene expression; genetic regulation; genetic regulatory element; genetically modified animals; human tissue; hypoxia; laboratory mouse; laboratory rabbit; nucleic acid probes; posttranslational modifications; protein structure function; stress proteins; tissue /cell culture; transcription factor; transfection; vascular endothelium

DESCRIPTION (Adapted from applicant's abstract and specific aims): This is a competitive renewal application of a grant funded in January 1993 to characterize a specific and unique set of endothelial cell (EC) stress proteins upregulated during acute and/or chronic hypoxia. The initial project theorized that these proteins, termed hypoxia associated proteins (HAPs), might contribute to the remarkable ability of EC to maintain cellular and functional integrity during various hypoxic conditions and proposed studies to characterize these HAPs. In this funding period, the investigators sequenced and identified two of the HAPs, determined their endothelial and stress specificity, explored their possible functions, investigated their regulation and determined their existence both ex vivo and in vivo. To characterize the HAPs further, explore their existence in more biologically relevant systems and develop cellular and animal models as a means to determine their function and significance, the specific aims will: 1) Identify the remaining HAPs; 2) Investigate regulation of HAPs by defining the site of gene regulation, the cis-acting regulatory elements and trans-acting factors responsible for altered gene expression; 3) Examine the effect of altering HAPs expression on the response to hypoxia in vitro using transfection techniques and antisense oligonucleotide to increase or decrease HAPs expression in cells that do contain them and to express HAPs in cells that do not normally contain them; and 4) Examine the production and role of HAPs in vivo in normal mice during hypoxia and by development of transgenic animals.

描述（根据申请人的抽象和具体目标改编）：这是 1993 年 1 月资助的赠款竞争性更新申请 表征一组特定且独特的内皮细胞 (EC) 应激 急性和/或慢性缺氧期间蛋白质上调。 最初的 该项目推测这些蛋白质被称为缺氧相关蛋白质 （HAP），可能有助于 EC 维持的卓越能力 各种缺氧条件下的细胞和功能完整性 提出的研究来表征这些 HAP。 在本次资助期内， 研究人员对其中两个 HAP 进行了测序和鉴定，确定了它们的 内皮和应激特异性，探索它们可能的功能， 研究它们的调节并确定它们的存在离体 和体内。 为了进一步描述 HAP 的特征，探索它们的存在 更多生物学相关系统并开发细胞和动物模型 确定其功能和意义、具体目标的手段 将： 1) 识别剩余的 HAP； 2) 通过以下方式调查 HAP 的监管 定义基因调控位点、顺式作用调控元件和 负责改变基因表达的反式作用因子； 3) 检查 改变 HAPs 表达对体外缺氧反应的影响 转染技术和反义寡核苷酸以增加或 减少含有 HAP 的细胞中的 HAP 表达并表达 HAP 在通常不包含它们的细胞中； 4) 检查生产 正常小鼠缺氧期间 HAP 的体内作用以及通过发育 转基因动物。