Taipei Medical University Institutional Repository:Item 987654321/4968
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 45073/58249 (77%)
Visitors : 2379512      Online Users : 164
RC Version 7.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://libir.tmu.edu.tw/handle/987654321/4968


    Title: cAMP依賴性的蛋白激酶對過度糖化最終產物誘導 RAW264.7吞噬細胞iNOS表現和NO產生的調控
    Involvement of cAMP Dependent Protein Kinase in BSA- AGEs-induced iNOS Expression and Nitric Oxide Production in RAW 264.7 Macrophages
    Authors: 陳健民
    ChienMing CHEN
    Contributors: 醫學檢驗暨生物技術學研究所
    Keywords: 過度糖化最終產物
    一氧化氮
    吞噬細胞
    Advanced glycosylation end-products
    Nitric oxide
    RAW 264.7 macrophages
    Date: 2001
    Issue Date: 2009-09-10 17:22:08 (UTC+8)
    Abstract: 過度糖化最終產物(AGEs)是糖與蛋白質經非酵素反應及長時間修飾後的產物,它會影響結構和功能改變,並與高齡及長期糖尿病人常見的併發症,如退行性神經變化及糖尿病之腎及血管併發症有關。以前我們曾証明AGEs誘導C6 Glioma cells之iNOS表現可經由p38 MAPK路徑。本實驗主要探討cAMP依賴性蛋白激酶對於AGEs誘導RAW 264.7吞噬細胞 (RAW 264.7 細胞) iNOS表現和NO產生的調控作用。AGEs誘導RAW 264.7 細胞之iNOS表現和NO的產生隨著時間與劑量而增加,這種由AGEs誘導RAW 264.7 細胞產生NO和iNOS的表現可被蛋白激酶A (PKA)的抑制劑KT 5720 (1 M) 和H8 (10 M) 所抑制。PKA直接活化物dibutyryl cAMP (Bt2 cAMP) 於不同濃度刺激 RAW 264.7 細胞,結果隨著濃度增加而提升NO的產生和iNOS的表現。AGEs刺激細胞內cAMP的產生是隨著時間增長而持續增加。為了証明AGEs誘導NO的產生和iNOS的表現不是因LPS的污染,本實驗以不同濃度之LPS抑制劑 polymyxin B加入含AGEs之RAW 264.7 細胞,結果發現AGEs誘導NO的產生不會被 polymyxin B所影響,證實AGEs的作用與LPS不同。 AGEs可於RAW 264.7 細胞活化p38 MAPK的產生,此效果可被KT 5720 (1 M),H8 (10 M) 和SB 203580 (10 M) 所抑制。因此由實驗推測AGEs可造成cAMP增加,轉而活化PKA,結果使p38 MAPK活化最後造成iNOS表現與NO的產生。
    Advanced glycosylation end products (AGEs) have been implicated in the structural and functional alterations of proteins that occur during aging and long-term diabetes. Previously, we have demonstrated that p38 MAPK is involved in the AGEs-induced iNOS expression in C6 glioma cells. In the present study, roles of cAMP dependent protein kinase in AGEs-induced iNOS expression in RAW 264.7 macrophages were investigated. AGEs caused a dose- and time-dependent increase of nitric oxide (NO) accumulation and iNOS expression in murine RAW 264.7 macrophages. The AGEs-simulated NO production and iNOS expression was dose-dependently inhibited by the PKA inhibitor, KT 5720 (1 M) and H8 (10 M). Consistently, treatment of RAW264.7 macrophages with dibutyryl cAMP results in concentration-dependent NO release and iNOS induction. On the other hand, AGEs-stimulated cAMP production in RAW 264.7 cells was seen in 1 h and persisted for at least 24 h. The NO production was not affected by polymyxin B, a lipopolysaccharide (LPS) inhibitor, suggesting the NO production is not due to LPS contamination in the BSA-AGEs (AGEs) preparation. AGEs actived p38 MAP kinase in RAW 264.7 cells and this effect was blocked by KT 5720 (1 M), H8 (10 M) and SB 203580 (10 M). The p38 MAPK inhibitor (SB 203580) did not inhibit AGEs-induced cAMP accumulation. In conclusion, our data suggest that AGEs may increase intracellular cAMP, which in turn activates PKA and results in p38 MAPK activation, iNOS induction and NO production in RAW 264.7 macrophages.
    Data Type: thesis
    Appears in Collections:[ ] Dissertations/Theses

    Files in This Item:

    File Description SizeFormat
    摘要.doc29KbMicrosoft Word179View/Open
    摘要.pdf62KbAdobe PDF281View/Open
    摘要.ppt114KbMicrosoft Powerpoint315View/Open
    摘要.ps335KbPostscript107View/Open


    All items in TMUIR are protected by copyright, with all rights reserved.


    著作權聲明 Copyright Notice
    • 本平台之數位內容為臺北醫學大學所收錄之機構典藏,包含體系內各式學術著作及學術產出。秉持開放取用的精神,提供使用者進行資料檢索、下載與取用,惟仍請適度、合理地於合法範圍內使用本平台之內容,以尊重著作權人之權益。商業上之利用,請先取得著作權人之授權。

      The digital content on this platform is part of the Taipei Medical University Institutional Repository, featuring various academic works and outputs from the institution. It offers free access to academic research and public education for non-commercial use. Please use the content appropriately and within legal boundaries to respect copyright owners' rights. For commercial use, please obtain prior authorization from the copyright owner.

    • 瀏覽或使用本平台,視同使用者已完全接受並瞭解聲明中所有規範、中華民國相關法規、一切國際網路規定及使用慣例,並不得為任何不法目的使用TMUIR。

      By utilising the platform, users are deemed to have fully accepted and understood all the regulations set out in the statement, relevant laws of the Republic of China, all international internet regulations, and usage conventions. Furthermore, users must not use TMUIR for any illegal purposes.

    • 本平台盡力防止侵害著作權人之權益。若發現本平台之數位內容有侵害著作權人權益情事者,煩請權利人通知本平台維護人員([email protected]),將立即採取移除該數位著作等補救措施。

      TMUIR is made to protect the interests of copyright owners. If you believe that any material on the website infringes copyright, please contact our staff([email protected]). We will remove the work from the repository.

    Back to Top
    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback