Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis.
Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogenesis.
复制标题
早产儿视网膜病变和病理性血管生成模型中 Presenilin-2 (PS2) 表达上调。
DOI：
10.1097/00001756-200101220-00019
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发表时间：
2001
期刊：
影响因子：
1.7
通讯作者：
Bazan,NG
中科院分区：
文献类型：
--
作者：
Lukiw,WJ;Gordon,WC;Rogaev,EI;Thompson,H;Bazan,NG
早老素-2 （PS2; AD4）是中枢神经系统发育和细胞命运决定过程中细胞间信号的调节因子，似乎参与了β-淀粉样蛋白前体蛋白（βAPP）转化为具有潜在神经毒性的β-淀粉样蛋白（a β）肽的致病过程。PS2基因启动子含有相对罕见的缺氧诱导转录因子HIF-1的多个DNA结合位点，这表明PS2的表达可能是氧可用性降低的敏感指标。我们使用循环缺氧/高氧（10-50% O2）方案，然后正常缺氧（20% O2）作为早产儿视网膜病变的视网膜模型，以诱导大鼠幼崽的新生血管（NV）。缺氧幼鼠的视网膜细胞核提取物显示HIF-1-DNA结合显著增加，随后延迟（2-7天）PS2 RNA信息和蛋白升高。缺氧时PS2基因的激活可能指导细胞命运走向病变血管生成和细胞间PS2介导的信号功能障碍。
Presenilin-2 (PS2; AD4), a regulator of intercellular signaling during CNS development and cell fate determination, appears to be involved in pathogenic processing of β-amyloid precursor protein (βAPP) into potentially neurotoxic β-amyloid (Aβ) peptides. The PS2 gene promoter contains multiple DNA binding sites for the relatively rare hypoxia-inducible transcription factor HIF-1, suggesting that PS2 expression may be a sensitive indicator of decreased oxygen availability. We have used a cycled hypoxia/hyperoxia (10–50% O2) protocol followed by normoxia (20% O 2) as a retinal model of retinopathy of prematurity to induce neovascularization (NV) in rat pups. Retinal cell nuclear extracts from pups undergoing hypoxia exhibited a dramatic increase in HIF-1-DNA binding, followed by a delayed (2–7 day) elevation of PS2 RNA message and protein. PS2 gene activation during hypoxia may direct cellular fate towards pathoangiogenesis and intercellular PS2-mediated signaling dysfunction.