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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 蘇銘嘉(Ming-Jai Su) | |
dc.contributor.author | Ting-Hsuan Li | en |
dc.contributor.author | 李庭萱 | zh_TW |
dc.date.accessioned | 2021-06-16T23:50:45Z | - |
dc.date.available | 2014-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-20 | |
dc.identifier.citation | 1 David R Janero & Haamid M. Sharif. Hydroperoxide-induced oxidative stress impairs heart muscle cell carbohydrate metabolism. Am. J. Physiol.266, C179-C188 (1990).
2 Kloner R. A. & Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation80, 1115-1127, doi:10.1161/01.cir.80.5.1115 (1989). 3 Pryor W. Oxy-radicals and related species: Their formation,lifetimes, and reactions. Rev. Physiol.48, 657-667 (1986). 4 Shoei-Sheng Lee & Hsih-Chin Yang. Isoquinoline alkaloids from Neolitsea. Journal of the chinese chemical society39 (1992). 5 M. J. Su & Lee. Thaliporphine, a positive inotropic agent with a negative chronotropoc action. Eur. J. Pharmacol.254, 141-150 (1994). 6 Hung L.M. & M.J. Su. Thaliporphine protects ischemic and ischemic-reperfused rat hearts via an NO-dependent mechanism. Drug Development Research52, 446-453 (2001). 7 Szu-Jan Yang & M.J. Su. Investigation of cardioprotective effects of TM1-1 against ischemia-reperfusion injury and the pharmacological effects in vascular system(Master thesis). (2005). 8 Wei-Luen Chang, Lee S. S. & Su M. J. Attenuation of post-ischemia reperfusion injury by thaliporphine and morphine in rat hearts. J. Biomed. Sci.12, 611-619 (2005). 9 Wei-Luen Chang & M.J. Su. Evaluation of TM-1on the inflammatory response in ischemia-reperfusion hearts (Internal report). (2006). 10 Chi-HsuanChen & M.J.Su. Evaluation of the cardiovascular and cardioprotective effects of the thaliporphine derivative against ischemia-reperfusion injury(Master thesis). (2011). 11 Rao F & Kuang S. J. Involvement of Src in L-type Ca2+ channel depression induced by macrophage migration inhibitory factor in atrial myocytes. . Mol Cell Cardiol47, 586–594 (2009). 12 Kimes BW & Brandt BL. Properties of a clonal muscle cell line from rat heart. Exp. Cell Res.98, 367–381 (1976). 13 Goldberg, Dunning & Bunn. Regulation of erythropoietin gene: evidence that the oxygen sensor is a heme protein. Sci. Justice242, 1412-1415 (1988). 14 Zou W. et al. Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP-1 activation. . J. Neurosci. Res.64, 646-653 (2001). 15 Xi L., Taher M., Yin C., Salloum F & Kukreja R. C. Cobalt chloride induces delayed cardiac preconditioning in mice through selective activation of HIF-1a and AP-1 and iNOS signaling. Am. J. Physiol.287, H2369-H2375 (2004). 16 Kotake-Nara E & Saida K. Endothelin-2/vasoactive intestinal contractor: regulation of expression via reactive oxygen species induced by CoCl2 and biological activities including neurite outgrowth in PC12 cells. Sci. World J6, 176-186 (2006). 17 Gaitanaki C & Beis I. CoCl2 induces protective events via the p38-MAPK signalling pathway and ANP in the perfused amphibian heart. J. Exp. Biol.210, 2267-2277 (2007). 18 DR Janero. Hydroperoxide-induced oxidative stress impairs heart muscle cell carbohydrate metabolism. Am. J. Physiol. (1994). 19 Boulton TG & Yancopoulos GD. ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell65, 663-675. (1991). 20 Su B & Karin M. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr. Opin. Immunol.8, 402-411 (1996). 21 Sun Bing & Sun, X.-B. Isorhamnetin inhibits H2O2-induced activation of the intrinsic apoptotic pathway in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK inactivation. J. Cell. Biochem.113, 473-485 (2012). 22 Guo Wen-yi & Li Fei. Akt-centered amplification loop plays a critical role in vascular endothelial growth factor/stromal cell-derived factor 1-alpha cross-talk and cardioprotection. Chin. Med. J. (Engl).124, 3800-3805 (2011). 23 Canan G. Nebigil & Luc Maroteaux. Serotonin is a novel survival factor of cardiomyocytes mitochondria as a target of 5-HT2B receptor signaling. The FASEB Journal 17, 1373-1375 (2003). 24 Klaus-Dieter Schluter & Hans Michael Piper. in Cell Culture Techniques. 25 Kantor S & Bagdy G. Increased wakefulness, motor activity and decreased theta activity after blockade of the 5-HT2B receptor by the subtype-selective antagonist SB-215505. Br. J. Pharmacol.142, 1332-1342 (2004). 26 P.R. Twentyman & M. Luscombe. Study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity. Br. J. Cancer56, 279-285 (1987). 27 Bianchi P. Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Circulation112, 3297-3305 (2005). 28 Bing Sun & Xiao-Bo Sun. Isorhamnetin Inhibits H2O2-Induced Activation of the Intrinsic Apoptotic Pathway in H9c2 Cardiomyocytes Through Scavenging Reactive Oxygen Species and ERK Inactivation. J. Cell. Biochem.113, 473-485 (2012). 29 Juliano L. & Thomas Michel. Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis. PNAS108, 15792–15797 (2011). 30 Youngho Jang & Zhelong Xu. Postconditioning preventsreperfusion injury by activating delta-opioid receptors. Anesthesiology108, 243-250 (2008). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65564 | - |
dc.description.abstract | 簡介:TM-1-1 (NTU-A) 和 TM-1-1-DP (NTU-A-DP) 是由aporphine alkaloid 類合成而來的兩個衍生物。在過去的研究中,TM-1-1 (NTU-A) 和 TM-1-1-DP (NTU-A-DP)已在缺血再灌流的動物實驗中發現許多的心臟保護作用。這些保護作用包括:減少梗塞面積、減少發炎物質的釋放以及活化具有心臟保護功效的eNOS和ERK等蛋白。且具有兩個磷酸根的TM-1-1-DP (NTU-A-DP) 又比 TM-1-1 (NTU-A) 擁有更好的水溶性與安全性。然而,他們的分子保護機制以及彼此間的差異尚未釐清。
方法與材料:我們使用成年SD大鼠的初代心室細胞作為主要的細胞模式,來排除其他非心肌細胞的干擾與模擬生理狀態。我們也使用氯化亞鈷與過氧化氫等化學物質在細胞模式上模擬缺血時的細胞缺氧狀態以及再灌流之氧化壓力。 實驗結果與討論:我們首先發現 TM-1-1 (NTU-A) 和 TM-1-1-DP (NTU-A-DP)對初代心室細胞有促進eNOS和ERK活化的初步效果。TM-1-1 (NTU-A) 和 TM-1-1-DP (NTU-A-DP)也有潛力透過5-HT2B receptor相關路徑提升因過氧化氫而降低的細胞存活率。雖然同樣是提升細胞存活率,我們發現TM-1-1 (NTU-A) 和 TM-1-1-DP (NTU-A-DP)是透過不一樣的路徑:TM-1-1 (NTU-A) 可以透過5-HT2B receptor的活化而降低caspase 3 的活性與增加細胞的存活率;TM-1-1-DP (NTU-A-DP)則可能透過 PI3K/AKT/eNOS的訊息傳遞路徑增加細胞的存活率。然而,一些與5-HT2B receptor不相關或與NO訊息傳遞不相關的路徑以及其他細節還需要後續更深入的探討。 | zh_TW |
dc.description.abstract | M 1-1 (NTU-A) and TM 1-1-DP (NTU-A-DP) are two synthetic derivatives of aporphine alkaloid. They had been found to afford various cardioprotective effects on ischemia-reperfusion model in vivo including a reduction of infarct size, inflammatory cytokines and an activation of cardioprotective proteins such as eNOS and ERK with better water solubility and safety for the later compound. However, the molecular mechanisms of their beneficial effects and differences haven’t been fully investigated. In order to elucidate their possible protective pathways on myocyes, we isolated primary cardiomyocytes to exclude interferences from non-myocytes and tried to gain better access to physiological or pathological condition in vivo. In the present study, primary ventricular cardiomyocytes were isolated from adult male Sprague-Dawley rats as a main cell model in vitro. Besides, hydrogen peroxide was administered to mimic the oxidative stress produced during reperfusion, which imposed a major injury to ischemia-reperfused hearts. Here, we found a preliminary effect of NTU-A and NTU-A-DP to induce eNOS and ERK activations in cultured ventricular cardiomyocytes, which had been proven in vivo. NTU-A and NTU-A-DP also showed a potential to maintain cell viability after H2O2-induced oxidative stress via the activation of 5-HT2B receptor-related pathway. Moreover, NTU-A can reduce caspase 3 activity and increase cell viability via the activation of 5-HT2B receptor; and NTU-A-DP may increase cell survival by stimulation of PI3K/AKT/eNOS signaling pathway via the activation of 5-HT2B receptor. Whereas, the involvement of 5-HT2B receptor-independent, NO-independent pathways and other details require further investigation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:50:45Z (GMT). No. of bitstreams: 1 ntu-101-R99443002-1.pdf: 48753534 bytes, checksum: ce434a586aaf0be20f92ddc705bc6803 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 論文口試委員審定書 I
誌謝 II 摘要 IV Abstract VI Index VIII Index for figures XII Introduction: 1 Ischemia-reperfusion injury 1 Thaliporphine and its derivatives 2 Appropriate source of cardiomyocyte 4 Cell models 5 Possible molecular pathways 7 eNOS 7 ERK 8 PI3K/AKT 9 5-HT 9 Aim 11 Materials and Methods 12 Culture of primary adult rat ventricular cardiomyocytes 12 Treatments of cells 14 Cell viability assessment 17 Protein extraction and Western Blot Analysis 18 Apoptosis Antibody Array 18 Intracellular Reactive Oxygen Species (ROS) Detection 19 Nitric Oxide Fluorometric Assay 19 Statistical analysis 20 Results: 21 Result1: Effect of NTU-A, NTU-A-DP and metformin on the phosphorylation of ERK and eNOS. 21 Result2: Concentration-dependent reduction of cell viability by H2O2 in cultured rat ventricular cells. 21 Result3: Comparison of the protective activity of NTU-A, NTU-A-DP, and Resveratrol against H2O2 -induced cell death 22 Result4: Role of NO production on cell viability of cultured rat ventricular cells in control, H2O2 -treated or H2O2 combined with NTU-A or NTU-A-DP treated condition. 23 Result5: Effect of NTU-A or NTU-A-DP on CoCl2-induced cell death of cultured rat ventricular cells 24 Result6: Interaction between serotonin and NTU-A or NTU-A-DP in protection of H2O2-induced cell death of cultured rat ventricular cells 24 Result7: Effect of 5-HT2A, 5-HT2B and 5-HT4 antagonists on the protective activity of NTU-A and NTU-A-DP in cultured rat ventricular cells 25 Result8: Effect of NTU-A and NTU-A-DP on H2O2-induced increase of caspase3 activity 26 Result9: Apoptosisantibody array analysis of the effect of NTU-A and NTU-A-DP on H2O2-induced activation of TNF-family death receptors signaling. 26 Result10: H2O2 – induced intracellular ROS production incardiomyocytes. 27 Result11: Effect of H2O2, NTU-A and NTU-A-DP on NO release in the cultured plasma of cardiomyocytes. 28 Result12: Effect of NTU-A, NTU-A-DP on the activation of eNOS, ERK, AKT and PI3K in culture rat ventricular cells under H2O2 treatment 29 Discussions 50 Conclusion 55 Future perspective 57 1. Fine time-course for NTU-A and NTU-A-DP intervention 57 2. Profile of detailed downsreamproapoptotic protein expression 57 3. The possible protective effects of 5-HT on cardiomyocyteswith the combination of MAOI and SSRI 58 4. The possible involvement ofδ-opioid receptor signaling in the protective effect of NTU-A-DP 58 5. Assessment of possible difference between MTT assay and Annexin V apoptosis analysis 59 Reference 60 Supplemental Data 63 | |
dc.language.iso | en | |
dc.title | TM-1-1 和 TM-1-1-DP 對於成年大鼠初代心肌細胞之心臟保護及抗氧化力 | zh_TW |
dc.title | Cardioprotective and Antioxidant Effects of TM-1-1 and TM-1-1-DP on Primary Adult Rat Ventricular Cardiomyocytes | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 顏茂雄(Mao-Hsiung Yen),林正一(Cheng-I Lin),陳文彬(Wen-Pin Chen) | |
dc.subject.keyword | Thaliporphine衍生物,初代成年大鼠心室細胞,過氧化氫所引發的氧化壓力,eNOS,L-NAME,5-HT2B receptor,SB-215505, | zh_TW |
dc.subject.keyword | Thaliporphine derivatives,Primary adult rat ventricular cardiomyocytes,hydrogen peroxide-induced oxidative stress,eNOS,L-NAME,5-HT2B receptor,SB-215505, | en |
dc.relation.page | 65 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-07-20 | |
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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