https://scholars.lib.ntu.edu.tw/handle/123456789/188538
Title: | 氧化低密度脂蛋白誘發動脈粥狀硬化之致病機轉─內皮細胞氧化低密度脂蛋白受體LOX-1之訊息傳遞機制(3/3) | Other Titles: | Oxidized LDL signaling through the endothelial receptor- LOX-1 (3/3) | Authors: | 李啟明 | Keywords: | 氧化低密度脂蛋白;內皮細胞功 能失調;動脈粥狀硬化;內皮細胞氧化低 密度脂蛋白受體;ox-LDL;endothelial dysfunction;atherosclerosis;LOX-1 | Issue Date: | 2002 | Publisher: | 臺北市:國立臺灣大學醫學院內科 | Abstract: | 氧化低密度脂蛋白(ox-LDL)是誘發血 管內皮細胞功能失調及動脈粥狀硬化之重 要原因之一。以往認為氧化密度脂蛋白經 巨噬細胞的清道夫受器攝取後才引發內皮 細胞病變。然而經實驗顯示,在缺乏巨噬 細胞的狀態下,氧化密度脂蛋白 能直接作 用於內皮細胞而引發功能失全。近來血管 內皮細胞被發現本身具有一種清道夫受器 - 內皮細胞氧化低密度脂蛋白受體 (LOX-1) ,能攝取氧化密度脂蛋白。LOX-1 由一個類似lectin 的胞外分域、胞膜穿透分 域、以及胞內分域三者所構成。到目前為 止, LOX-1 和ox-LDL 結合後對內皮細胞 中蛋白質活性及基因表現的影響還不是很 清楚。本計畫目的在瞭解ox-LDL 誘發血管 內皮細胞功能失調的分子機制。我們以 LOX-1 為餌,藉由酵母菌雙雜交法(Yeast two hybrid screen),從人類心臟cDNA library 中釣到15 個會和LOX-1 交互作用的 基因。 更進一步,我們藉由微陣列分析 (microarray analysis),從人類的臍靜脈內皮 細胞(HUVEC)中,找到39 個基因,其表現 會因ox-LDL 的刺激而改變。找出這些基 因,將有助於我們瞭解ox-LDL 對血管內皮 細胞功能的影響,更進一步對治療動脈硬 化疾病的新要開發有所助益。 Oxidative modification of low-density lipoprotein (ox-LDL) is crucial in the pathogenesis of endothelial dysfunction, which is a major characteristic of atherosclerosis. Similar to that of macrophage, vascular endothelial cells can internalize ox-LDL. The recognition and uptake of ox-LDL in endothelial cells is different from that of macrophage in that it is mediated by LOX-1, a C-type lectin-like scavenger receptor. To date, the physiological effects of LOX-1 on protein activities and gene expression levels after it binds ox-LDL and internalizes into endothelial cells are still unclear. Our aim for this project was to investigate the molecular mechanism of endothelial cell dysfunction caused by ox-LDL. We first did yeast two-hybrid screen using the N-terminal domain of LOX-1 (LOX-1N) as the bait. Fifteen genes whose protein products interact with LOX-1N were cloned from a human heart cDNA library. Furthermore, we did microarray analysis and found in HUVEC cells 39 genes whose expression levels were changed after ox-LDL stimulation. Identification of these genes will help us understand the molecular effect of ox-LDL on endothelial cell function and discover new drugs for the treatments of atherosclerosis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/29783 | Other Identifiers: | 902320B002162M52 | Rights: | 國立臺灣大學醫學院內科 |
Appears in Collections: | 醫學系 |
File | Description | Size | Format | |
---|---|---|---|---|
902320B002162M52.pdf | 51.33 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.