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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 呂紹俊 | |
| dc.contributor.author | Ya-Hsin Lan | en |
| dc.contributor.author | 藍雅馨 | zh_TW |
| dc.date.accessioned | 2021-06-13T07:55:59Z | - |
| dc.date.available | 2006-08-04 | |
| dc.date.copyright | 2005-08-04 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-07-23 | |
| dc.identifier.citation | 姚文雅（2003）脂多醣類刺激RAW264.7細胞resistin基因表現增加時分子機制的探討。
臺灣大學醫學院生物化學暨分子生物研究所碩士論文 陳嘉綾（2004）順位因子Octamer參與脂多醣類刺激RAW264.7細胞resistin基因表現之探討。 臺灣大學醫學院生物化學暨分子生物研究所碩士論文 Aguirre, V., Uchida, T., Yenush, L., Davis, R., and White, M. F. (2000). The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 275, 9047-54. Ahima, R. S., and Flier, J. S. (2000). Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11, 327-32. Almqvist, J., Zou, J., Linderson, Y., Borestrom, C., Altiok, E., Zetterberg, H., Rymo, L., Pettersson, S., and Ernberg, I. (2005). Functional interaction of Oct transcription factors with the family of repeats in Epstein-Barr virus oriP. J Gen Virol 86, 1261-7. Andersen, B., and Rosenfeld, M. G. (2001). POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev 22, 2-35. Banerjee, R. R., and Lazar, M. A. (2001). 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36288 | - |
| dc.description.abstract | 2001年，resistin因其作用可能與胰島素抗阻（insulin resistance）相關而得名，然而之後許多研究resistin與肥胖及第二型糖尿病的關聯性顯示不一致的實驗結果，到目前為止的研究成果推論出resistin可能參與調控血糖恆定、脂肪生成分化和發炎反應。
本實驗室以lipopolysaccharide（LPS）處理小鼠巨噬細胞RAW264.7發現resistin mRNA表現增加，探討其分子機制的實驗結果顯示resistin promoter-996至-969的28bp和-914至-907的octamer區域（element）皆為LPS促進resistin promoter轉錄活性的重要反應序列。接續已知的研究結果，利用resistin promoter-996~-969及-927~-896兩段DNA鹼基對分別作為探針（probe）進行凝膠電泳位移分析（EMSA），兩種探針都會與RAW264.7細胞核萃取液特異性結合形成DNA/protein複合物，其中-984至-979（CTATCT）互補股序列為GATA區域，EMSA及啟動子活性分析實驗結果顯示GATA區域並不參與LPS誘導resistin promoter活性增加，resistin promoter -996~-969中的LPS重要反應序列仍需要以不同方式去探討。而-914至-907（ATTTGCAT）為octamer區域，利用未標定的-927~-896 bp或consensus octamer oligonucleotides都可以競爭掉探針與核蛋白質的結合，但若將未標定的-927~-896 bp中ATTGCAT改變成GCCGCAT作為抑制物，則競爭能力明顯下降。目前已知有兩種octamer element binding proteins Oct-1及Oct-2，RT-PCR及西方墨點法的實驗結果顯示Oct-1和Oct-2 mRNA及蛋白質在RAW264.7細胞皆有表現，且處理過LPS的RAW264.7細胞中Oct-2 mRNA和蛋白質表現有顯著增加的現象，Oct-1則沒有明顯變化。利用biotin-labeled-octamer探針與streptavidin磁球結合，再與RAW264.7細胞核萃取液結合，得到與octamer結合的蛋白質進行西方墨點法分析，結果顯示Oct-2的確與octamer區域結合，且經過LPS處理的細胞核萃取液Oct-2結合至octamer區域有增加的情形。ChIP assay的結果也顯示在in vivo狀態，LPS會活化Oct-2結合於resistin promoter。Reporter assay中利用Oct-1或Oct-2或GATA-2表現質體與pResistin(-996/+61)-Luc一起轉染RAW264.7細胞，結果顯示Oct-2可以提高LPS促進resistin promoter的活性，相對的Oct-1卻有抑制性的作用，GATA-2則沒有影響。實驗室之前的結果指出LPS增加resistin表現可被MEK或PI3K或p38的抑制劑（U0126、Ly294002及SB203580）所抑制，Oct-2表現質體與pResistin(-996/+61)-Luc一起轉染的RAW264.7細胞，LPS引起的resistin promoter轉錄活性會被U0126及Ly294002抑制73 %及90 %，而轉染pResistin (-968/+61)-Luc的細胞，LPS所增加的luciferase也同樣被U0126及Ly294002抑制67 %及89 %。綜合以上結果，LPS調控Oct-2及另一未確認的因子來提高resistin基因的表現；LPS促進Oct-2 mRNA和蛋白質表現並經由PI3K和MEK途徑活化Oct-2蛋白質而增加resistin的轉錄作用。 | zh_TW |
| dc.description.abstract | Resistin is named for resistance to insulin. Studies so far suggest that resistin may involve glucose homeostasis, adipogenesis and inflammatory response.
From our previous studies, LPS increases resistin expression in vivo and in vitro. LPS also increases resistin mRNA expression in RAW264.7 cells, a mouse macrophage-like cell line. Our previous results showed that an octamer (ATTTGCAT) element, located at -914 to -907, and an unidentified element, within -996 to -969, are essential for maximal promoter activity in response to LPS stimulation. Two resistin promoter fragments, -996~-969 bp and -927∼-896 bp, were 32P-labeled and used as probe in EMSA assays, the results showed that both probes could form specific DNA/protein complexes with nuclear proteins from RAW264.7 cell. Cold -927∼-896 fragment and consensus octamer oligonucleotides completely competed for the formation of DNA/protein complex using the -927~-896 probe; however, octamer mutant probe (ATTTGCAT→GCCTGCAT) only partially competed the formation of the DNA/protein complex. Two nuclear proteins, Oct-1 and Oct-2, are known octamer-binding proteins. To identify which of them is involved in LPS induced resistin gene expression, we first checked whether Oct-1 and Oct-2 are expressed in RAW264.7. Both Oct-1 and Oct-2 mRNAs (detected by RT-PCR) and proteins (detected by Western blotting) are detectable in RAW264.7. However, only Oct-2 mRNA and protein levels were significant up-regulated by LPS in RAW264.7. Binding of Oct-2 in RAW264.7 nuclear extracts to the resistin promoter were demonstrated by using biotinylated -927~-896 bp DNA fragment captured by streptavidin magnetic beads and Chromatin immunoprecipitation (ChIP) assay. Co-transfection of RAW264.7 with pResistin(-996/+61)-Luc and pCG-Oct-1 and/or pCG-Oct-2 further demonstrated that Oct-2, but not Oct-1, is responsible for the activation of resistin promoter upon LPS treatment. Taken together, our results showed that both -996~-969 bp and the octamer element located at -914 to -907, are essential for maximal promoter activity in response to LPS stimulation. In addition, we found that Oct-2, but not Oct-1, is responsible for LPS activation of resistin promoter. We also found, for the first time, that mRNA and protein levels of Oct-2 were significantly up-regulated by LPS in RAW264.7 cells, and activation of Oct-2 may involve PI3K and MEK pathways. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T07:55:59Z (GMT). No. of bitstreams: 1 ntu-94-R92442025-1.pdf: 949219 bytes, checksum: 3b812694c39e464673b85558183be608 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | 中文摘要1
英文摘要2 縮寫對照表3 第一章緒論6 第一節 文獻回顧7 第二節 研究動機與實驗目的16 第二章材料與方法18 第一節 實驗材料19 第二節 小鼠巨噬細胞RAW264.7細胞株之培養21 第三節 小鼠resistin promoter定點突變之報導基因質體之建構21 第四節 大量製備pCG-Oct1, pCG-Oct2, pCG, pCEP4-GATA2及 pCEP4表現質體26 第五節 Resistin promoter活性之分析26 第六節 RAW264.7細胞中Oct-1和Oct-2的表現情形28 第七節 Resistin promoter與RAW264.7細胞核萃取液結合狀況32 第八節 Oct-2與RAW264.7細胞中resistin promoter的結合情形36 第三章實驗結果40 第一節 Resistin promoter -996~-969 bp參與LPS誘導resistin基因表現41 第二節 Oct-2與resistin promoter -927至-896 bp結合情形42 第三節 Oct-1、Oct-2與GATA-2過量表現對LPS誘導resistin promoter轉錄活性的影響44 第四章討論46 第一節 Resistin與發炎反應的關係47 第二節 LPS調節resistin promoter轉錄活性的機制48 第三節 總結53 第五章圖表54 第六章參考文獻71 | |
| dc.language.iso | zh-TW | |
| dc.subject | 脂多醣 | zh_TW |
| dc.subject | RAW264.7 | en |
| dc.subject | resistin | en |
| dc.subject | Oct-2 | en |
| dc.subject | LPS | en |
| dc.title | 轉錄因子Oct-2參與脂多醣刺激RAW264.7細胞resistin基因表現之研究 | zh_TW |
| dc.title | Oct-2 transcription factor is involved in the regulation of LPS-induced resistin gene expression in RAW264.7 cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 姜安娜,張淑芬,楊偉勛,許金玉 | |
| dc.subject.keyword | 脂多醣, | zh_TW |
| dc.subject.keyword | RAW264.7,LPS,resistin,Oct-2, | en |
| dc.relation.page | 82 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-07-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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