博碩士論文 100224015 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:10 、訪客IP:3.215.182.81
姓名 張崇人(Chung-jen Chang)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 酸敏感G蛋白偶合受體-TDAG8在發炎性疼痛中所扮演的角色
(Roles of T-cell Death-Associated Gene 8 in Inflammatory Pain)
相關論文
★ 週邊發炎反應增加酸敏感受體- TDAG8基因在背根神經節之表現量★ 酸敏感G蛋白偶合受體,G2A,在ASIC3基因剔除小鼠中改變表現量
★ MrgB4受體專一表現於感覺神經元,且在ASIC3基因剔除小鼠中有不同的表現。★ 血清素受體2B對酸敏感離子通道3與辣椒素受體1的影響
★ 酸敏感G蛋白偶合受體在小鼠背根神經節神經元中的訊息傳導路徑★ 酸敏感G蛋白偶合受體功能上的拮抗機制
★ TDAG8活化後經由PKA與PKCε增強辣椒素受體的敏感度★ 台灣海岸植物之內生真菌多樣性研究
★ ASIC3、TRPV1或TDAG8基因缺失會減緩關節炎誘導的熱痛覺過敏並抑制衛星膠細胞表現★ 抑制OGR1表現可減緩慢性神經性疼痛藉由減少顆粒性白血球數及非IB4神經元之鈣訊號
★ 抑制OGR1及G2A表現可藉由調控非IB4神經元鈣訊號減緩酸所誘導長期疼痛★ G-蛋白偶合接受體與G-蛋白訊號調控蛋白之整合型資料庫
★ 血清素受體2B基因在酸敏感受體3基因剔除小鼠的背根神經節中表現量增加★ 酸敏感的G蛋白偶合受體─OGR1表現在背根神經節內與痛覺相關的感覺神經元上
★ 血清素受體2B參與血清素引起的機械性痛覺過敏★ 血清素受體2B調控鈣離子變化影響機械性痛覺敏感
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   [檢視]  [下載]
  1. 本電子論文使用權限為同意立即開放。
  2. 已達開放權限電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。
  3. 請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。

摘要(中) 長期發炎性疼痛主要是由於皮膚或軟組織受到傷害或是疾病引發的心肌缺血或癌症時所產生。其中內部受損的細胞與免疫細胞會釋放發炎相關介質:如蛋白酶、ATP、氫離子等,去活化或調控這些響應組織的傷害性受器,進而產生訊號並將這些訊號從週邊匯集於背根神經節(DRG)再傳到中樞系統最終傳回大腦,產生疼痛的感覺。然而局部的高濃度氫離子會產生組織酸化的現象,並透過酸敏感離子通道(Proton-sensing ion channel)或G蛋白偶合受體(Proton-sensing GPCR)去調控傷害性感覺神經元,因此被認為是造成疼痛的主要條件。在目前的研究中發現有四個酸敏感G蛋白偶合受體,OGR1、GPR4、G2A和TDAG8,皆會表現在背根神經節上參與疼痛相關的中小型直徑細胞;且亦知道當發炎時背根神經節上的T細胞死亡相關基因8 (TDAG8) 的表現量會增加。由於目前此方面的研究尚不清楚,因此推斷TDAG8與發炎性疼痛是否有直接性的相關聯。在本篇論文中,我利用了RNAi干擾技術來抑制TDAG8的基因表現,並探討TDAG8在疼痛中的功能為何。根據我的結果發現降低TDAG8基因與蛋白質的表現可以完全抑制酸所誘導的機械性痛覺過敏感現象;而由完全弗氏佐劑與海藻醣所引發的長期發炎性痛覺過敏感現象也同樣會受到抑制。透過以上的結果可以表明TDAG8是參與在發炎性疼痛中的。
摘要(英) Chronic inflammatory pain results from inflammation in the skin or soft tissues in response to tissue injury, ischemia or cancer growth. The damaged cells and immune cells release inflammatory mediators such as proteases, ATP and proton to activate or modulate nociceptors, leading to pain. Tissue acidosis (high proton concentration) is the major factor to cause pain by activating proton-sensing ion channels and G-protein-coupled receptors (GPCRs). Four proton-sensing GPCRs, OGR1, GPR4, G2A, and T-cell death-associated gene 8 (TDAG8), are identified and expressed in pain-relevant loci, the dorsal root ganglia (DRG) and TDAG8 expression is increased in inflamed DRG. However, it remains unclear whether TDAG8 is involved in inflammatory pain. In this study, I used the shRNA technique to inhibit TDAG8 gene expression and explore TDAG8 function in pain. I have found that reduction of TDAG8 gene and protein expression completely inhibited acid-induced mechanical hyperalgesia. Hyperalgesia induced by CFA or carrageenan was also reduced. These results suggested that TDAG8 is involved in inflammatory pain.
關鍵字(中) ★ 酸敏感G蛋白偶合受體
★ 發炎性疼痛
★ 長期發炎性疼痛
★ T細胞死亡相關基因8
關鍵字(英) ★ proton-sensing GPCRs
★ inflammatory pain
★ Chronic inflammatory pain
★ TDAG8
論文目次 摘要 III
Abstract IV
第一章 緒論 1
1.1 痛覺 (Pain) 2
1.2痛覺訊息傳遞路徑 (Nociceptive pathway) 3
1.3發炎性疼痛 (Inflammatory pain) 4
1.3.1 組織酸化 (Tissue acidosis) 5
1.3.2 氫離子 (Proton) 5
1.4 G蛋白偶合受體 (G-protein-coupled receptors;GPCR) 6
1.4.1 結構與下游反應路徑 (Structure and downstream signaling pathways) 7
1.4.2 酸敏感G蛋白偶合受體 (Proton sensing G-protein-coupled receptors) 8
1.4.3 TDAG8受體 (T-cell Death-Associated Gene 8) 9
1.5 研究動機與目的 10
第二章 實驗材料與方法 11
2.1 實驗材料 12
2.1.1 菌株 12
2.1.2 細胞株 12
2.1.3 核醣核酸干擾 (RNA interference) 12
2.1.4 實驗動物 12
2.1.5 實驗藥品 13
2.2 實驗方法 13
2.2.1 大腸桿菌的轉型作用 (Transformation) 13
2.2.2 細菌的培養 (Grow bacterial) 14
2.2.3 表現質體的製備 14
2.2.3.1 小量的製備 (Mini-prep.) 14
2.2.3.2 中量的製備 (Midi-prep.) 15
2.2.4 表現質體的確認 15
2.2.4.1 限制酵素分析 15
2.2.4.2 瓊脂醣膠的製備及電泳 16
2.2.5 細胞培養 (Cell culture) 16
2.2.6 轉染作用 (Transfection) 17
2.2.7 流氏細胞儀分析TDAG8沉默效率 (Knockdown efficiency) 17
2.2.8 基因表現分析 18
2.2.8.1 細胞核醣核酸的萃取 18
2.2.8.2 DNase I純化處理 19
2.2.8.3 微量組織核醣核酸的萃取 19
2.2.8.4 染色體去氧核醣核酸 (Genomic DNA) 汙染檢測 20
2.2.8.5 cDNA的合成 20
2.2.9 聚合酶連鎖反應 (Polymerase chain reaction, PCR) 21
2.2.9.1 反轉錄-聚合酶連鎖反應 (Reverse transcription PCR, RT-PCR) 21
2.2.9.2 同步定量聚合酶連鎖反應系統 (Quantitative PCR, Q-PCR) 21
2.2.10 分析細胞內部cAMP的累積情況 22
2.2.10.1 cAMP 收集 22
2.2.10.2 ELISA (The enzyme-linked immunosorbent assay) 22
2.2.11細胞內鈣離子濃度分析 23
2.2.11.1 玻片的前處理 23
2.2.11.2 鈣離子成像分析法 (Calcium image) 24
2.2.12 組織切片的製作 25
2.2.12.1 玻片的處理置備 25
2.2.12.2 組織包埋及冷凍組織切片及固定 25
2.2.13 免疫染色 (Immunohistochemistry) 25
2.2.14 發炎性疼痛動物模式 26
2.2.15 RNAi 干擾抑制發炎性疼痛 27
2.2.15.1 注射陽離子明膠與TDAG8-shRNA質體的復合物 27
2.2.15.2 抑制發炎性疼痛動物模式 27
2.2.16 痛覺行為測試 (Animals behavior test) 28
2.2.17 小鼠腳掌腫脹測量 29
2.2.18 統計分析 29
第三章 結果 30
3.1 TDAG8受到shTDAG8-cherry-A1、B1、C1的沉默(Knockdown)效率 31
3.2 酸性刺激下細胞內cAMP的累積受到TDAG8基因沉默影響而減少 32
3.3 在酸(pH5.5)刺激下,細胞內鈣離子濃度因 TDAG8沉默現象而減少 34
3.4 TDAG8基因大部分分佈於中小型直徑的DRG神經元 34
3.5 shTDAG8-cherry-B1質體會表現在中小型直徑的DRG神經元 35
3.6 shTDAG8-cherry-B1會降低小鼠體內TDAG8的基因表現 36
3.7 抑制TDAG8表現會降低酸引發的機械性痛覺過敏感現象 37
3.8 抑制TDAG8表現會降低完全弗氏佐劑引發的機械性痛覺過敏感現象 38
3.9 抑制TDAG8表現可以達到長期減緩痛覺過敏感現象 39
3.10 抑制TDAG8的表現無法降低完全弗氏佐劑所引發的腫脹現象 40
3.11 shTDAG8-cherry-A1同樣會降低完全弗氏佐劑引發的疼痛 40
3.12 抑制TDAG8表現會降低海藻醣引發的機械性痛覺過敏感 41
3.13 PKCɛ抑制劑對於抑制TDAG8所減緩的機械性痛覺過敏感有加成效果 41
第四章 討論 43
4.1 TDAG8在酸性的刺激下是以活化Gs蛋白來傳遞下游訊號 45
4.2 B1能有效的抑制小鼠體內的TDAG8基因並完全降低酸所引發的疼痛 46
4.3 TDAG8參與完全弗氏佐劑引發的長期機械性疼痛 48
4.3.1 發炎的前期 (0-3小時) 49
4.3.2 發炎的中期至後期 (>4小時-16天) 50
第五章 參考文獻 52
附錄 61
圖3-1. shTDAG8-A1、B1、C1 質體圖譜 62
圖3-2. TDAG8受到shTDAG8-A1、B1、C1的沉默(Knockdown)效率 64
圖3-3. 酸性刺激下細胞內cAMP的累積受到TDAG8基因沉默影響而減少 67
圖3-4. 在酸(pH5.5)刺激下,細胞內鈣離子釋放因 TDAG8沉默現象而減少 69
圖3-5. TDAG8基因大部分分佈於中小型直徑的DRG神經元 71
圖3-6. shTDAG8-B1質體會表現在中小型直徑的DRG神經元 73
圖3-7. shTDAG8-B1會降低小鼠體內TDAG8的基因表現 75
圖3-8. 抑制TDAG8表現會降低酸引發的機械性痛覺過敏感現象 77
圖3-9. 抑制TDAG8表現會降低完全弗氏佐劑引發的機械性痛覺過敏感現象 80
圖3-10. 抑制TDAG8表現可以減緩完全弗氏佐劑引發的長期慢性疼痛 82
圖3-11. 抑制TDAG8的表現無法降低完全弗氏佐劑所引發的腫脹現象 84
圖3-12. shTDAG8-A1同樣會降低完全弗氏佐劑引發的機械性痛覺過敏感現象 85
圖3-13. 抑制TDAG8表現會降低海藻醣引發的機械性痛覺過敏感現象 87
圖3-14. PKCɛ抑制劑對於抑制TDAG8所減緩的機械性痛覺過敏感有加成效果 89
附錄一、溶液、緩衝液及其他藥劑配方 91
附表一 95
附圖 S-1. 流式細胞儀圈選分析細胞與螢光值校正 98
參考文獻 1. Akaike N., Krishtal, O.A. and Maruyama, T., (1990). Proton-induced sodium current in frog isolated dorsal root ganglion cells. J. Neurophysiol. 63, pp. 805-813.
2. Aley KO, Levine JD (1999). Role of protein kinase A in the maintenance of
inflammatory pain. J Neurosci. May 15;19(6):2181-6.
3. Andrew D. and Greenspan J. D., (1999). Mechanical and heat sensitization of
cutaneous nociceptors after peripheral inflammation in the rat. J. Neurophysiol.,
Nov;82(5):2649-56.
4. Aley, KO, Messing, RO, Mochly-Rosen, D, Levine, JD (2000). Chronic
hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J Neuro sci. 20(12):4680-5.
5. Aley, KO, Martin A, McMahon T, Mok J, Levine JD, Messing Ro. (2001). Nociceptor sensitization by extracellular signal-regulated kinase. J Neurosci.Sep 1;21(17):6933-9.
6. Alvarez-de-la Rosa, D., Zhang, P., Shao, D., White, F. and Canessa, C.M., (2002).
Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc. Natl. Acad. Sci. U. S. A. 99, pp.2326–2331.
7. Amadesi S, Cottrell GS, Divino L, Chapman K, Grady EF, Bautista F, Karanjia R,
Barajas-Lopez C, Vanner S, Vergnolle N, Bunnett NW (2006). Protease-activated
receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent
mechanisms in rats and mice. Sep 1;575(Pt 2):555-71
8. Bevan S, and Yeats J. (1991). Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones. J Physiol. Feb 433:145-61.
9. Booden MA, Siderovski DP, Der CJ. (2002). Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA. Mol Cell Biol. 2002 Jun;22(12):4053-61.
10. Bhave G, and Gereaum RW 4th. (2004). Posttranslational mechanisms of peripheral sensitization. J Neurobiol. 2004 Oct;61(1):88-106
11. Black J. A., Liu S., Tanaka M., Cummins T R., and Waxman S G., (2004). Change in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Proc. Natl. Acad. Sci. USA, 108, pp. 237-247.
12. Basbaum AI, Bautista DM, Scherrer G, Julius D. (2009) Cellular and molecular mechanisms of pain. Cell. Oct 16;139(2):267-84.
13. Choi JW., Lee SY., Choi Y. (1996). Identification of a putative G protein-
coupled receptor induced during activation-induced apoptosis of T cells. Cell Immunol. Feb 25;168(1):78-84.
14. Chen, C.C., England, S., Akopian, A.N. and WooD, J.N., (1998). A sensory neuron-specific, proton-gated ion channel. Proc. Natl. Acad. Sci. U. S. A. 95, pp. 10240-10245.
15. Costigan M. and Woolf C. J., (2000). Pain: Molecular mechanisms. J. Pain., Sep 1; (3 Suppl) pp.35-44
16. Caterina M. J., Leffler A., Malmberg A. B., Martin W. J., Trafton J., Petersen-
Zeitz K. R., Koltzenburg M., Basbaum A. I. and Julius D., (2000). Impaired Nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, Apr 14 pp. 306-313.
17. Casey JR., Grinstein S., Orlowski J. (2001). Sensors and regulators of intracellular pH. Nat Rev Mol Cell Biol. Jan 11;(1):50-61
18. Chen YJ, Huang CW, Lin CS, Chang WH, Sun WH. (2009). Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain. Mol Pain. Jul 14;5:39.
19. Casey GJ, Jolley D, Phuc TQ, Tinh TT, Tho DH, Montresor A, Biggs BA. (2010). Long-term weekly iron-folic acid and de-worming is associated with stabilised haemoglobin and increasing iron stores in non-pregnant women in Vietnam. PLoS One. 2010 Dec 30;5(12):e15691.
20. Dray A, Urban L, Dickenson A (1994). Pharmacology of chronic pain. Trends Pharmacol Sci. 1994 Jun;15(6):190-7.
21. Dray, A. (1995). Inflammatory mediators of pain. Br J Anaesth. Aug; 75(2): 125-31.
22. Decaris E, Guingamp C, Chat M, Philippe L, Grillasca JP, Abid A, Minn A, Gillet P, Netter P, Terlain B (1999). Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation. Arthritis Rheum. Sep;42(9):1951-60.
23. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A & Sheardown SA (2000). Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature May 11 ; 405 (6783):183-7
24. Dina OA, Khasar SG, Gear RW, Levine JD. (2009). Activation of Gi induces mechanical hyperalgesia poststress or inflammation. Neuroscience. May 5;
160(2):501-7.
25. Escoubas, P., Weille, J.R.D., Lecoq, A., Diochot, S., Waldmann, R., Champigny, G., Moinier, D., Me´nez, A. and Lazdunski, M., (2000). Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels. J. Biol. Chem. 275, pp. 25116–25121.
26. Eglen RM., Bosse R., Reisine T. (2007). Emerging concepts of guanine nucleotide-binding protein-coupled receptor (GPCR) function and implications for high throughput screening. Assay Drug Dev Technol. Jun;5(3):425-51.
27. Fukunaka Y, Iwanaga K, Morimoto K, Kakemi M, Tabata Y. (2002). Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation. J Control Release. Apr 23;80(1-3):333-43.
28. Hunt S.P., and Mantyh P. W., (2001). The molecular dynamics of pain control. Nat Rev Neurosci. Feb;2(2):83-91.
29. Hucho T.B., Dina O. A., Levine J. D., (2005). Epac mediates a cAMP- to PKC signaling in inflammatory pain: an ioslection B4 (+) neurons-specific mechanism. J Neurosci. Jun 29;25(26):6119-26.
30. Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH. (2007). Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors. Mol Cell Neurosci. Oct;36(2):195-210.
31. Hang LH, Yang JP, Yin W, Wang LN, Guo F, Ji FH, Shao DH, Xu QN, Wang XY, Zuo JL. (2012). Activation of spinal TDAG8 and its downstream PKA signaling pathway contribute to bone cancer pain in rats. Eur J Neurosci. Jul; 36(1): 2107 -17
32. Ishii S1, Kihara Y, Shimizu T. (2005). Identification of T cell death-associated gene 8 (TDAG8) as a novel acid sensing G-protein-coupled receptor. J Biol Chem. Mar 11;280(10):9083-7.
33. Im DS. (2005). Two ligands for a GPCR, proton vs lysolipid. Acta Pharmacol Sin. Dec;26(12):1435-41.
34. Ihara Y1, Kihara Y, Hamano F, Yanagida K, Morishita Y, Kunita A, Yamori T, Fukayama M, Aburatani H, Shimizu T, Ishii S. (2010). The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor. Proc Natl Acad Sci U S A. Oct 5;107(40):17309-14.
35. Julius, D. and Basbaum, A.I. (2001). Molecular mechanisms of nociception. Nature 413, 203-210.
36. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB. (2004). Acid- induced pain and its modulation in humans. J Neurosci. Dec 1;24(48):10974-9.
37. Krishtal and Pidoplichko, (1981). A "receptor" for protons in small neurons of trigeminal ganglia: possible role in nociception. Neurosci Lett. Jul 17;24(3) : 243-6
38. Kandel E.R., Schwartz J.H. and Jessell, T.M., Principles of neural science. 4th edition. Chapter 24.
39. Konnerth, A., Lux, H.G. Morad, M., (1987). Proton-induced transformation of calcium channel in chick dorsal root ganglion cells. J Physiol. May;386:603-33.
40. Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K.H, (2003). Proton-sensing G-protein-coupled receptors. Nature Sep 4;425(6953):93-8.
41. Malmberg AB, Brandon EP, Idzerda RL, Liu H, McKnight GS, Basbaum AI. (1997). Diminished inflammation and nociceptive pain with preservation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase. J Neurosci. Oct 1;17(19):7462-70
42. Murakami N, Yokomizo T, Okuno T, Shimizu T. (2004). G2A is a proton- sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. J Biol Chem. Oct 8;279(41):42484-91
43. McCudden CR, Hains MD, Kimple RJ, Siderovski DP, Willard FS. (2005). G-protein signaling: back to the future. Cell Mol Life Sci. Mar;62(5):551-77.
44. Nagakura Y1, Okada M, Kohara A, Kiso T, Toya T, Iwai A, Wanibuchi F, Yamaguchi T. (2003). Allodynia and hyperalgesia in adjuvant-induced arthritic rats: time course of progression and efficacy of analgesics. J Pharmacol Exp Ther. Aug;306(2):490-7
45. Probst WC, Snyder LA, Schuster DI, Brosius J, Sealfon SC. (1992). Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol. Jan-Feb;11(1):1-20.
46. Parada CA, Reichling DB, Levine JD. (2005). Chronic hyperalgesia priming in the rat involves a novel interaction between cAMP and PKCε second messenger pathway. Pain. Jan;113(1-2):185-90.
47. Radu CG, Yang LV, Riedinger M, Au M, Witte ON (2004). T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci U S A. Jan 6;101(1):245-50.
48. Radu CG., Nijagal A., McLaughlin J., Wang L., Witte ON. (2005). Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc Natl Acad Sci U S A. Feb 1;102(5):1632-7.
49. Radu CG., Cheng D., Nijagal A., Riedinger M., McLaughlin J., Yang LV., Johnson J., Witte ON. (2006). Normal immune development and glucocorticoid
-induced thymocyte apoptosis in mice deficient for the T-cell death-associated gene 8 receptor. Mol Cell Biol. Jan;26(2):668-77.
50. Reeh, P. W., and Steen, K. H. (1996). Tissue acidosis in nociception and pain. Brain Research, 113,143-151.
51. Roos A., Boron WF. (1981). Intracellular pH. Physiol. Apr;61(2):296-434.
52. Strader CD1, Fong TM, Graziano MP, Tota MR. (1995). The family of G-protein-coupled receptors. FASEB J. Jun;9(9):745-54.
53. Steen KH, Steen AE, Kreysel HW, Reeh PW. (1996). Inflammatory mediators potentiate pain induced by experimental tissue acidosis. Pain. Aug;66(2-3):
163-70.
54. Sautel M and Milligan G. (2000). Molecular manipulation of G-protein-coupled receptors: a new avenue into drug discovery. Curr Med Chem. Sep;7(9):889-96.
55. Sluka KA, Kalra A, Moore SA. (2001). Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve. Jan; 24(1):37-46.
56. Scholz J, and Woolf CJ. (2002). Can we conquer pain? Nat Neurosci. Nov;5 Suppl:1062-7
57. Taiwo YO, Levine JD, Burch RM, Woo JE, Mobley WC. (1991). Hyperalgesia induced in the rat by the amino-terminal octapeptide of nerve growth factor. Proc Natl Acad Sci U S A. Jun 15;88(12):5144-8
58. Tosa N1, Murakami M, Jia WY, Yokoyama M, Masunaga T, Iwabuchi C, Inobe M, Iwabuchi K, Miyazaki T, Onoe K, Iwata M, Uede T. (2003). Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis. Int Immunol. 2003 Jun;15(6):741-9
59. Thakor D, Spigelman I, Tabata Y, Nishimura I. (2007). Subcutaneous peripheral injection of cationized gelatin/DNA polyplexes as a platform for non-viral gene transfer to sensory neurons. Mol Ther. Dec;15(12):2124-31.
60. Wang JQ1, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F. (2004). TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. J Biol Chem. Oct 29;279(44):45626-33.
61. Wang L, Radu CG, Yang LV, Bentolila LA, Riedinger M, Witte ON. (2005). Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A . Mol Biol Cell. May;16(5):2234-47.
62. Yang LV, Radu CG, Wang L, Riedinger M, Witte ON. (2005). Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. Blood. Feb 1;105(3):1127-34.
63. Zhang X, Li L, McNaughton PA. (2008). Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron. Aug 14;59(3):450-461.
指導教授 孫維欣(Wei-hsin Sun) 審核日期 2014-7-8
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明