ENDOTHELIAL CELL HYPOXIA ASSOCIATED PROTEINS

描述（根据申请人的摘要和具体目标改编）：这是 1993年1月资助的一项赠款的竞争性续延申请， 表征一组特定和独特的内皮细胞（EC）应激 在急性和/或慢性缺氧期间上调的蛋白质。 初始 该项目的理论是，这些蛋白质，称为缺氧相关蛋白质， （HAPs），可能有助于EC维持 在各种低氧条件下的细胞和功能完整性， 建议研究这些HAP的特征。 在这段时间内， 研究人员对其中两种HAP进行了测序和鉴定， 内皮和应激特异性，探讨其可能的功能， 研究了它们的调节，并确定了它们的存在， 和体内。 为了进一步描述HAP，探索它们在 更多的生物相关系统，并开发细胞和动物模型， 一种确定其功能和意义的手段， 将：1）确定剩余的HAP; 2）调查HAP的监管， 定义基因调控位点，顺式作用调控元件， 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来增加或 降低含有HAP的细胞中HAP的表达，并表达HAP 在通常不含它们的细胞中;和4）检查生产 和HAPs在正常小鼠体内缺氧时的作用， 转基因动物

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.