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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧哲明(Che-Ming Teng) | |
| dc.contributor.author | Li-Lin Huang | en |
| dc.contributor.author | 黃麗霖 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:17:38Z | - |
| dc.date.available | 2006-08-31 | |
| dc.date.copyright | 2006-08-31 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-24 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32867 | - |
| dc.description.abstract | 在粥狀動脈硬化初期，氧化態低密度脂蛋白 (oxidized low density lipoprotein，oxLDL) 和內皮細胞之反應扮演著重要的角色。轉錄因子HIF-1的活性增加會導致下游調控的基因增加，這些基因可以參與在能量代謝適應、細胞存活和增生、血管新生、細胞侵入和轉移以及血管張力等病理疾病的過程中。
在本篇實驗中，我們發現到oxLDL (200μg/ml) 會誘使內皮細胞株ECV304中HIF-1α蛋白質增加。由luciferase reporter gene assay中，我們也確定了oxLDL會使HIF-1活性增加的現象。然而，本篇實驗中我們也發現到oxLDL並不會影響HIF-1α的轉錄作用，也無影響pVHL蛋白質表現和與ubiquitin結合的HIF-1α的分解層面中。 當我們投與激酶的抑制劑，譬如wortmannin (100 nM)、rapamycin (100 nM)、manumycin A (1μM) 和PD98059 (50μM)，皆可以有效地減少oxLDL誘導HIF-1活性增加的現象。由西方點墨法，我們看到oxLDL可以活化Akt和ERK以及它們下游的激酶蛋白，如mTOR、S6K、4EBP 和eIF-4E，由這些實驗結果可以知道oxLDL是有參與在HIF-1α蛋白質形成的轉譯作用中。更進一步地，我們利用dominant-negative (DN) transfection的技術，送入DN-Akt 和DN-Ras 發現都能有效的抑制由oxLDL所造成HIF-1α蛋白質增加的結果。綜合上述的實驗結果，在人類臍靜脈內皮細胞株ECV304中，oxLDL可以增加轉錄因子HIF-1的活性和HIF-1α蛋白質合成，主要是經由調控PI3K/Akt和 Ras/ERK這兩條訊息傳遞途徑而來。因此，轉錄因子HIF-1在oxLDL所造成的粥狀動脈硬化病程中，扮演著重要的角色。 | zh_TW |
| dc.description.abstract | Oxidized low density lipoprotein (oxLDL) and endothelial cells play central roles in the early stage of atherosclerosis. Increased HIF-1 activity leads to upregulation of genes that are involved in many aspects of pathological diseases, including metabolic adaptation, cell survival/proliferation, angiogenesis, invasion/metastasis and vascular tone.
In this study, we demonstrated that oxLDL (200μg/ml) induced hypoxia-inducible factor-1α(HIF-1α) protein accumulation in human endothelial cell line (ECV304) under normoxic condition. HIF-1-dependent luciferase reporter gene analysis underscored HIF-1 transactivation. OxLDL has no effect on HIF-1α transcriptional and degradational levels, including pVHL protein expression and association with ubiquitin. OxLDL-induced HIF-1αactivity was attenuated by the pretreatment with wortmannin (100 nM), rapamycin (100 nM), manumycin A (1 μM) and PD98059 (50 μM). Western blotting analysis showed that oxLDL induced the phosphorylation of Akt , ERK and their downstream protein kinases, including mTOR, S6K, 4EBP and eIF-4E, which served to regulate HIF-1α expression at translational step. Moreover, transfection of a dominant-negative vector of Akt or Ras resulted in abolishing the HIF-1αproduction triggered by oxLDL. These results indicated that oxLDL induced HIF-1-dependent reporter gene activation and HIF-1α accumulation in ECV304 via PI3K/Akt and Ras/ERK pathways. These findings may suggest a role of HIF-1 in atherosclerosis and oxLDL-induced pathogenesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:17:38Z (GMT). No. of bitstreams: 1 ntu-95-R93443008-1.pdf: 6064879 bytes, checksum: 6e37292efb9a2a44127e2aeb59c12755 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 縮寫表………………………………………………………….1
中文摘要……………………………………………………….3 英文摘要……………………………………………………….5 緒論 一.文獻回顧……………………………………………….7 二.研究動機與目的……………………………………...33 實驗材料與方法………………………………………….......35 實驗結果……………………………………………………...47 討論…………………………………………………………...55 結論與未來展望……………………………………………...64 圖表…………………………………………………………...65 參考文獻……………………………………………………...80 | |
| dc.language.iso | zh-TW | |
| dc.subject | HIF-1α | zh_TW |
| dc.subject | 氧化態低密度脂蛋白 | zh_TW |
| dc.subject | HIF-1α | en |
| dc.subject | oxLDL | en |
| dc.title | 探討oxLDL在人類臍帶靜脈內皮細胞ECV304經由調控PI3K/Akt 和Ras/ERK途徑來活化 hypoxia-inducible factor-1α的作用機轉 | zh_TW |
| dc.title | OxLDL Activates Hypoxia-Inducible Factor-1α in Human Umbilical Vein Endothelial Cell Line ECV304 through PI3K/Akt and Ras/ERK Pathways | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃德富(Tur-Fu Huang),顧記華(Jih-Hwa Guh),顏茂雄(Mao-Hsiung Yen),楊春茂(Chuen-Mao Yang) | |
| dc.subject.keyword | 氧化態低密度脂蛋白,HIF-1α, | zh_TW |
| dc.subject.keyword | oxLDL,HIF-1α, | en |
| dc.relation.page | 93 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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