跳到主要內容

臺灣博碩士論文加值系統

(3.235.120.150) 您好!臺灣時間:2021/08/03 05:10
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:王騰懋
研究生(外文):Teng-Mao Wang
論文名稱:SYN-4對大白鼠血管平滑肌細胞鈣離子濃度的調節作用
論文名稱(外文):SYN-4 Modulated Cytosolic Ca2+ Levels in Rat Vascular Smooth Muscle Cells
指導教授:古宏海汪貴珍汪貴珍引用關係
指導教授(外文):Hung-Hai KuGuei-Jane Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:69
中文關鍵詞:鈣離子血管平滑肌細胞鈣離子通道
外文關鍵詞:calciumvascular smooth muscle cellcalcium channel
相關次數:
  • 被引用被引用:0
  • 點閱點閱:94
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
SYN-4 為大花咸豐草萃取之活性化合物經官能基修飾後的衍生物,預試驗得知其具有良好的血管舒張活性,可能具有調控細胞質鈣離子濃度的能力。本研究中以培養的大白鼠血管平滑肌細胞及內皮細胞,探討 SYN-4 對細胞質鈣離子濃度的調節作用。實驗結果顯示 SYN-4 本身不影響平滑肌細胞質鈣離子的濃度,但前處理後能抑制平滑肌與內皮細胞經 G protein coupled receptor (GPCR) –phospholipase C (PLC)- inositol 1,4,5-triphosphate (IP3)- IP3 receptor (IP3R) 造成之內鈣釋放,此作用並非經由抑制 ligand 與 GPCR 的結合,也非作用在抑制IP3R活性。SYN-4 抑制 SOCC 活化的作用可經抑制內鈣釋放來達成,而此 SOCCv並非 NSCC 類型。SYN-4v能活化 non-selective cation channels (NSCC) 類型之receptor operated channels (ROCC),增加外鈣流入細胞。此作用與 store operated Ca2+ channels (SOCC) 或voltage operated Ca2+ channels (VOCC) 無關。Fetal calf serum (FCS) 含多種生長因子,主要經由vGPCR-PLC-IP3-IP3R 造成鈣離子濃度變化,SYN-4雖能減少此鈣離子濃度變化,但無法抑制平滑肌細胞的生長,對平滑肌細胞也無毒性。此外,我們也發現 SYN-4 能抑制 VOCC 活化。研究結果顯示 SYN-4 同時調節平滑肌細胞內鈣與外鈣,可能是經由 G protein signaling crosstalk pathway 機制達成。至於 SYN-4 在內皮細胞能幫助活化 ROCC,使細胞質鈣離子濃度上升,可能因此活化 eNOS,產生 NO,而導致血管舒張作用。
SYN-4, an analogue of one compound derived from Bidens pilosa, was found to have potent vasorelaxing effect on modulating cytosolic calcium concentration in our previous study. Experiments were performed to determine the role of SYN-4 on cytosolic calcium movement in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) isolated from rat thoracic aorta. The basal cytosolic calcium concentration was unaffected by SYN-4. Results show that pretreatment of SYN-4 could inhibit intracellular calcium release and increase extracellular calcium influx in VSMCs and ECs. Intracellular calcium release was triggered by G protein coupled receptor (GPCR)– phosholipase C (PLC)- inositol 1,4,5-triphosphate (IP3)- IP3 receptor (IP3R) pathway. SYN-4 inhibited intracellular calcium release neither by affecting ligand binding to GPCR, nor by affecting IP3R activity. The inhibition of store operated Ca2+ channels (SOCC) was through an intracellular calcium decrement mechanism. The SOCC was not NSCC type channels. Its was also found that SYN-4 enhance the activation of receptor operated channels (ROCC) and increase calcium influx, but neither SOCC nor voltage operated Ca2+ channels (VOCC) was involved. The characteristic of ROCC modulated by SYN-4 was non-selective cation channels (NSCC) type. Fetal calf serum (FCS) stimulated cytosolic calcium concentration changes by the GPCR-PLC-IP3-IP3R pathway. SYN-4 attenuated FCS induced calcium mobilization, but did not affect cell proliferation and had no toxicity on VSMCs. Taken together, the mechanisms of SYN-4 affecting calcium influx and release may be routed through the G protein signaling crosstalk pathway in VSMCs. On the other hand, SYN-4 modulated Ca2+ fluxes directly through ROCC and thus, produced NO by activating eNOS in ECs.
第五章、參考文獻
Austin C, Wray S. Interactions between Ca2+ and H+ and functional consequences in vascular smooth muscle. Circ Res 86: 355-363, 2000.
Bates DO, Curry FE. Vascular endothelial growth factor increases microvascular permeability via a Ca2+-dependent pathway. Am J Physiol 273: H687-694, 1997.
Berk BC, Corson MA. Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases. Circ Res 80: 607-616, 1997.
Boeynaems JM, Pearson JD. P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms. Trends Pharmacol Sci 11:34-37, 1990.
Bootman MD, Collins TJ, Peppiatt CM, Prothero LS, MacKenzie L, De Smet P, Travers M, Tovey SC, Seo JT, Berridge MJ, Ciccolini F, Lipp P. Calcium signaling-an overview. Semin Cell Dev Biol 12: 3-10, 2001.
Brieger A, Trojan J, Raedle J, Plotz G, Zeuzem S. Transient mismatch repair gene transfection for functional analysis of genetic hMLH1 and hMSH2 variants. Gut 51: 677-684, 2002.
Burnstock G. Purinergic signaling and vascular cell proliferation and death. Arterioscler Thromb Vasc Biol 22: 364-373. 2002.
Chin TY, Chueh SH. Distinct Ca2+ signalling mechanisms induced by ATP and sphingosylphosphorylcholine in porcine aortic smooth muscle cells. Br J Pharmacol 129: 1365-1374, 2000.
Choi S, Lovinger DM. Metabotropic glutamate receptor modulation of voltage-gated Ca2+ channels involves multiple receptor subtypes in cortical neurons. J Neurosci 16: 36-45,1996.
Cohen RA, Weisbrod RM, Gericke M, Yaghoubi M , Bierl B, Bolotina VM. Mechanism of nitric oxide–induced vasodilatation refilling of intracellular stores by sarcoplasmic reticulum Ca2+-ATPase and inhibition of store-operated Ca2+ influx. Circulation 84: 210-219, 1999.
Dimo T, Rakotonirina S, Kamgang R, Tan PV, Kamanyi A, Bopelet M. Effects of leaf aqueous extract of Bidens pilosa (Asteraceae) on KCl- and norepinephrine-induced contractions of rat aorta. J Ethnopharmacol 60: 179-182, 1998.
Di Virgilio F, Solini A. P2 receptors: new potential players in atherosclerosis. Br J Pharmacol 135: 831-842, 2002.
Dudek SM, Birukov KG, Zhan X, Garcia JG. Novel interaction of cortactin with endothelial cell myosin light chain kinase. Biochem Biophys Res Commun 298: 511-519, 2002.
Filo RS, Bohr DF, Ruegg JC. Glycerinated skeletal and smooth muscle: calcium and magnesium dependence. Science 147: 1581-1583, 1965.
Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 98: 1662-1666, 2001.
Ganado P, Ruiz E, Del Rio M, Larcher F, Sanz M, Steinert JR, Tejerina T. Growth inhibitory activity of indapamide on vascular smooth muscle cells. Eur J Pharmacol 428: 19-27, 2001.
Gloeckner H, Jonuleit T, Lemke HD. Monitoring of cell viability and cell growth in a hollow-fiber bioreactor by use of the dye Alamar Blue. J Immunol Methods 252: 131-138, 2001.
Gollasch M, Haase H, Ried C, Lindschau C, Morano I, Luft FC, Haller H. L-type calcium channel expression depends on the differentiated state of vascular smooth muscle cells. FASEB J 12: 593-601, 1998.
Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450, 1985.
Guh JH, Yu SM, Ko FN, Wu TS, Teng CM. Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated from Angelica pubescens. Eur J Pharmacol 298: 191-197, 1996.
Hermans E, Challiss RA. Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors. Biochem J 359: 465-484, 2001.
Hirata A, Igarashi M, Yamaguchi H, Suwabe A, Daimon M, Kato T, Tominaga M. Nifedipine suppresses neointimal thickening by its inhibitory effect on vascular smooth muscle cell growth via a MEK-ERK pathway coupling with Pyk2. Br J Pharmacol 131: 1521-1530, 2000.
Inoue R, Okada T, Onoue H, Hara Y, Shimizu S, Naitoh S, Ito Y, Mori Y. The transient receptor potential protein homologue TRP6 is the essential component of vascular a1-adrenoceptor-activated Ca2+-permeable cation channel. Circ Res 88: 325-332, 2001.
Jan CR, Tseng CJ. MK-886, a leukotriene biosynthesis inhibitor, as an activator of Ca(2+) mobilization in Madin-Darby canine kidney (MDCK) cells. J Pharmacol Exp Ther 294: 96-102, 2000.
Kawanabe Y, Hashimoto N, Masaki T. Molecular mechanisms for the activation of Ca2+-permeable nonselective cation channels by endothelin-1 in C6 glioma cells. Biochem Pharmacol 65: 1435-1439, 2003.
Large WA. Receptor-operated Ca2+-permeable nonselective cation channels in vascular smooth muscle: a physiologic perspective. J Cardiovasc Electrophysiol 13: 493-501, 2003.
Lin CC, Shyr MH, Chien CS, Wang CC, Chiu CT, Hsiao LD, Yang CM.Thrombin-stimulated cell proliferation mediated through activation of Ras/Raf/MEK/MAPK pathway in canine cultured tracheal smooth muscle cells. Cell Signal 14: 265-275, 2002.
Ma HT, Favre CJ, Patterson RL, Stone MR, Gill DL.Ca2+ entry activated by S-nitrosylation. Relationship to store-operated Ca2+ entry. J Biol Chem 274: 35318-35324, 1999.
Ma HT, Patterson RL, van Rossum DB, Birnbaumer L, Mikoshiba K, Gill DL. Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels. Science 287: 1647-1651, 2000.
Marsigliante S, Elia MG, Di Jeso B, Greco S, Muscella A, Storelli C. Increase of [Ca2+]i via activation of ATP receptors in PC-Cl3 rat thyroid cell line. Cell Signal 14: 61-67, 2002.
Masuo M, Toyo-oka T, Shin WS, Sugimoto T. Growth-dependent alterations of intracellular Ca2+-handling mechanisms of vascular smooth muscle cells. PDGF negatively regulates functional expression of voltage-dependent, IP3-mediated, and Ca2+-induced Ca2+ release channels. Circ Res 69: 1327-1339, 1991.
Michel CC, Curry FE. Microvascular permeability. Physiol Rev 179: 703-761, 1999.
Murata T, Sato K, Hori M, Ozaki H, Karaki H. Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension. J Biol Chem. 277: 44085-44092, 2002.
Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664-666, 1988.
Patterson RL, van Rossum DB, Gill DL. Store-operated Ca2+ entry: evidence for a secretion-like coupling model. Cell 98: 487-499, 1999.
Purdy KE, Arendshorst WJ. Iloprost inhibits inositol-1,4,5-trisphosphate-mediated calcium mobilization stimulated by angiotensin II in cultured preglomerular vascular smooth muscle cells. J Am Soc Nephrol 12: 19-28, 2001.
Putney JW Jr, Bird GS. The inositol phosphate-calcium signaling system in nonexcitable cells. Endocr Rev 14: 610-631, 1993.
Putney JW Jr, McKay RR. Capacitative calcium entry channels. Bioessays 21: 38-46, 1999.
Schneider JC, El Kebir D, Chereau C, Lanone S, Huang XL, De Buys Roessingh AS, Mercier JC, Dall'Ava-Santucci J, Dinh-Xuan AT.Involvement of Ca2+/calmodulin-dependent protein kinase II in endothelial NO production and endothelium-dependent relaxation. Am J Physiol Heart Circ Physiol. 284: H2311-H2319, 2003.
Stepien O, Zhang Y, Zhu D, Marche P. Dual mechanism of action of amlodipine in human vascular smooth muscle cells. J Hypertens 20: 95-102, 2002.
Taniguchi H, Hirano H, Tanaka Y, Tanaka H, Shigenobu K. Possible involvement of Ca2+ entry and its pharmacological characteristics responsible for endothelium-dependent, NO-mediated relaxation induced by thapsigargin in guinea-pig aorta.
J Pharm Pharmacol. 51: 831-840, 1999.
Tsien RY, Pozzan T, Rink TJ. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol 94: 325-334, 1982.
Vallot O, Combettes L, Jourdon P, Inamo J, Marty I, Claret M, Lompre´ AM, Intracellular Ca2+ handling in vascular smooth muscle cells is affected by proliferation Thromb Vasc Biol 20: 1225-1235, 2000.
van Rossum DB, Patterson RL, Ma HT, Gill DL. Ca2+ entry mediated by store depletion, S-nitrosylation, and TRP3 channels. Comparison of coupling and function. J Biol Chem 275: 28562-28568, 2000.
Viard P, Exner T, Maier U, Mironneau J, Nurnberg B, Macrez N. Gbetagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase. FASEB J 13: 68594, 1999.
Wang GJ, Shan J, Pang PK, Yang MC, Chou CJ, Chen CF. The vasorelaxing action of rutaecarpine: direct paradoxical effects on intracellular calcium concentration of vascular smooth muscle and endothelial cells. J Pharmacol Exp Ther 276: 1016-1021, 1996.
Watanabe H, Takahashi R, Zhang XX, Kakizawa H, Hayashi H, Ohno R. Inhibition of agonist-induced Ca2+ entry in endothelial cells by myosin light-chain kinase inhibitor. Biochem Biophys Res Commun 225: 777-784, 1996.
Weirich J, Seiler L, Hug MJ, Fleckenstein-Grun G. Ca2+ entry into primary cultured pig coronary smooth muscle cells after previous store depletion by repetitive P2Y purinoceptor stimulation. Cell Calcium 29: 359-67, 2001.
Weisbrod RM, Griswold MC, Du Y, Bolotina VM, Cohen RA. Reduced responsiveness of hypercholesterolemic rabbit aortic smooth muscle cells to nitric oxide. Arterioscler Thromb Vasc Biol 17: 394-402, 1997.
Yang Z, Madinova A, Kozai T, Joch H, Aebi U, Luscher TF. Felodipine inhibits nuclear translocation of p42/44 mitogen-activated protein kinase and human smooth muscle cell growth. Cardiovasc Res 53: 227-231, 2002.
謝宗萬。 全國中草藥匯編(第二版), 人民衛生出版社,北京 1996。
楊國禎。 外來植物大車拼 (二), 網站:塔山自然實驗室塔山文集專欄,2001。
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 11. 辛旗,「對中國統一前景的幾點思考」,台北:中國論壇第三八四期,民國八十一年九月,頁4 - 11。
2. 10. 沈玄池,「歐洲聯盟共同外交暨安全政策體制與運作方式改革之研究」,《美歐季刊》,14:3,第139期,民國89年秋季,頁263-304。
3. 05. 邱垂泰、陳信甫,「新三個中國國際法主體的統一說」,全國律師月刊,第四卷第九期,台北:全國律師月刊,民國八十九年十一月,頁64-72。( 經全國律師月刊編輯委員會審查同意准釵A次添附注釋改寫刊登 )。
4. 04. 陳信甫,邱垂泰,「三個中國國際法主體的統一說」,中國論壇第三七五期( 聯合報系 ),民國八十年十二月,頁14-18。
5. 03. 邱垂泰,「兩岸關係何妨參考歐洲共同體模式」,中國論壇第三六五期( 聯合報系 ),民國八十年二月,頁102-106。
6. 02. 王玉葉,「歐洲聯盟之輔助原則」,《歐美研究》第三十卷第二期,民國八十九年六月,頁1-30。
7. 12. 周旭華,「歐洲共同體對外貿易關係的權力劃分問題」,美歐季刊,第十四卷四期,臺北:政大國際關係研究中心,民國八十九年冬季號,頁441以下。
8. 13. 周旭華,「歐洲共同體在GATT/ WTO體系下的談判及締約行為-法律面分析」,問題與研究月刊,第四十卷六期,臺北:政大國際關係研究中心,民國九十一年11-12月號,pp.101-125。
9. 14. 洪德欽,「歐元之法律分析」,歐美研究季刊第二十九卷第二期,台北:中央研究院歐美研究所,民國八十八年六月,頁171-272。
10. 15. 洪德欽,「歐洲中央銀行之對外關係」,美歐季刊第十三卷第三期,台北:政治大學國際關係研究中心,民國八十九年秋季號,頁305-331。
11. 18. 黃偉峰,「歐盟整合模式與兩岸主權爭議之解析」,《歐美研究》,第31卷第1期,2001年,頁129-173。
12. 20. 廖福特,人權宣言?人權法典?--「歐洲聯盟基本權利憲章」之分析,「歐洲聯盟重要法政議題」專號,歐美研究季刊:第31卷4期,民國90年.12月,頁689-751。
13. 24. 蘇宏達,「歐盟經驗與兩岸統合:建立WTO架構下的雙邊商務糾紛解決機制」,《問題與研究》第四十卷第二期,民國90年3月,頁1-32。