請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64936完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 詹東榮(Tong-Rong Jan) | |
| dc.contributor.author | Yi-Hsuan Lin | en |
| dc.contributor.author | 林宜萱 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:08:59Z | - |
| dc.date.available | 2017-08-10 | |
| dc.date.copyright | 2012-08-10 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-03 | |
| dc.identifier.citation | Batandier, C., Leverve, X., Fontaine, E., 2004. Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I. The Journal of biological chemistry 279, 17197-17204.
Brookes, P.S., Yoon, Y., Robotham, J.L., Anders, M.W., Sheu, S.S., 2004. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. American journal of physiology. Cell physiology 287, C817-833. Chen, Q., Vazquez, E.J., Moghaddas, S., Hoppel, C.L., Lesnefsky, E.J., 2003. Production of reactive oxygen species by mitochondria: central role of complex III. The Journal of biological chemistry 278, 36027-36031. Chen, Y., McMillan-Ward, E., Kong, J., Israels, S.J., Gibson, S.B., 2007. Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. Journal of cell science 120, 4155-4166. Circu, M.L., Aw, T.Y., 2010. Reactive oxygen species, cellular redox systems, and apoptosis. Free radical biology & medicine 48, 749-762. Cossarizza, A., Baccarani-Contri, M., Kalashnikova, G., Franceschi, C., 1993. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochemical and biophysical research communications 197, 40-45. Crompton, M., 1999. The mitochondrial permeability transition pore and its role in cell death. The Biochemical journal 341 ( Pt 2), 233-249. Cuperus, R., Leen, R., Tytgat, G.A., Caron, H.N., van Kuilenburg, A.B., 2010. Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma. Cellular and molecular life sciences : CMLS 67, 807-816. Danial, N.N., Gimenez-Cassina, A., Tondera, D., 2010. Homeostatic functions of BCL-2 proteins beyond apoptosis. Advances in experimental medicine and biology 687, 1-32. Datta, S.R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., Greenberg, M.E., 1997. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231-241. Garcia Fernandez, M.I., Ceccarelli, D., Muscatello, U., 2004. Use of the fluorescent dye 10-N-nonyl acridine orange in quantitative and location assays of cardiolipin: a study on different experimental models. Analytical biochemistry 328, 174-180. Garrido, C., Galluzzi, L., Brunet, M., Puig, P.E., Didelot, C., Kroemer, G., 2006. Mechanisms of cytochrome c release from mitochondria. Cell death and differentiation 13, 1423-1433. Gillessen, T., Grasshoff, C., Szinicz, L., 2002. Mitochondrial permeability transition can be directly monitored in living neurons. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 56, 186-193. Guzman, M., Sanchez, C., Galve-Roperh, I., 2002. Cannabinoids and cell fate. Pharmacology & therapeutics 95, 175-184. Indo, H.P., Davidson, M., Yen, H.C., Suenaga, S., Tomita, K., Nishii, T., Higuchi, M., Koga, Y., Ozawa, T., Majima, H.J., 2007. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage. Mitochondrion 7, 106-118. Iversen, L., 2003. Cannabis and the brain. Brain : a journal of neurology 126, 1252-1270. Jan, T.R., Su, S.T., Wu, H.Y., Liao, M.H., 2007. Suppressive effects of cannabidiol on antigen-specific antibody production and functional activity of splenocytes in ovalbumin-sensitized BALB/c mice. International immunopharmacology 7, 773-780. Kalivendi, S.V., Kotamraju, S., Cunningham, S., Shang, T., Hillard, C.J., Kalyanaraman, B., 2003. 1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide. The Biochemical journal 371, 151-164. Killestein, J., Hoogervorst, E.L., Reif, M., Blauw, B., Smits, M., Uitdehaag, B.M., Nagelkerken, L., Polman, C.H., 2003. Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis. Journal of neuroimmunology 137, 140-143. Kirkland, R.A., Adibhatla, R.M., Hatcher, J.F., Franklin, J.L., 2002. Loss of cardiolipin and mitochondria during programmed neuronal death: evidence of a role for lipid peroxidation and autophagy. Neuroscience 115, 587-602. Klein, T.W., Newton, C.A., 2007. Therapeutic potential of cannabinoid-based drugs. Advances in experimental medicine and biology 601, 395-413. Kokoszka, J.E., Waymire, K.G., Levy, S.E., Sligh, J.E., Cai, J., Jones, D.P., MacGregor, G.R., Wallace, D.C., 2004. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427, 461-465. Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., 2001. Mitochondrial permeability transition and oxidative stress. FEBS letters 495, 12-15. Kumarswamy, R., Seth, R.K., Dwarakanath, B.S., Chandna, S., 2009. Mitochondrial regulation of insect cell apoptosis: evidence for permeability transition pore-independent cytochrome-c release in the Lepidopteran Sf9 cells. The international journal of biochemistry & cell biology 41, 1430-1440. Lakhan, S.E., Rowland, M., 2009. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC neurology 9, 59. Le Bras, M., Clement, M.V., Pervaiz, S., Brenner, C., 2005. Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histology and histopathology 20, 205-219. Lee, C.Y., Wey, S.P., Liao, M.H., Hsu, W.L., Wu, H.Y., Jan, T.R., 2008. A comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells. International immunopharmacology 8, 732-740. Lemasters, J.J., Theruvath, T.P., Zhong, Z., Nieminen, A.L., 2009. Mitochondrial calcium and the permeability transition in cell death. Biochimica et biophysica acta 1787, 1395-1401. Ligresti, A., Moriello, A.S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L., Laezza, C., Portella, G., Bifulco, M., Di Marzo, V., 2006. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. The Journal of pharmacology and experimental therapeutics 318, 1375-1387. Liu, D.Z., Hu, C.M., Huang, C.H., Wey, S.P., Jan, T.R., 2010. Cannabidiol attenuates delayed-type hypersensitivity reactions via suppressing T-cell and macrophage reactivity. Acta pharmacologica Sinica 31, 1611-1617. Luchetti, F., Canonico, B., Mannello, F., Masoni, C., D'Emilio, A., Battistelli, M., Papa, S., Falcieri, E., 2007. Melatonin reduces early changes in intramitochondrial cardiolipin during apoptosis in U937 cell line. Toxicology in vitro : an international journal published in association with BIBRA 21, 293-301. Mackie, K., Stella, N., 2006. Cannabinoid receptors and endocannabinoids: evidence for new players. The AAPS journal 8, E298-306. Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R., Feldmann, M., 2000. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences of the United States of America 97, 9561-9566. Massi, P., Vaccani, A., Bianchessi, S., Costa, B., Macchi, P., Parolaro, D., 2006. The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. Cellular and molecular life sciences : CMLS 63, 2057-2066. Massi, P., Vaccani, A., Ceruti, S., Colombo, A., Abbracchio, M.P., Parolaro, D., 2004. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. The Journal of pharmacology and experimental therapeutics 308, 838-845. McKallip, R.J., Jia, W., Schlomer, J., Warren, J.W., Nagarkatti, P.S., Nagarkatti, M., 2006. Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression. Molecular pharmacology 70, 897-908. McMillin, J.B., Dowhan, W., 2002. Cardiolipin and apoptosis. Biochimica et biophysica acta 1585, 97-107. Mechoulam, R., Peters, M., Murillo-Rodriguez, E., Hanus, L.O., 2007. Cannabidiol--recent advances. Chemistry & biodiversity 4, 1678-1692. Murphy, M.P., 2009. How mitochondria produce reactive oxygen species. The Biochemical journal 417, 1-13. Narita, M., Shimizu, S., Ito, T., Chittenden, T., Lutz, R.J., Matsuda, H., Tsujimoto, Y., 1998. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proceedings of the National Academy of Sciences of the United States of America 95, 14681-14686. Nicoletti, I., Migliorati, G., Pagliacci, M.C., Grignani, F., Riccardi, C., 1991. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. Journal of immunological methods 139, 271-279. Orrenius, S., Gogvadze, V., Zhivotovsky, B., 2007. Mitochondrial oxidative stress: implications for cell death. Annual review of pharmacology and toxicology 47, 143-183. Paradies, G., Petrosillo, G., Pistolese, M., Ruggiero, F.M., 2002. Reactive oxygen species affect mitochondrial electron transport complex I activity through oxidative cardiolipin damage. Gene 286, 135-141. Peng, T.I., Jou, M.J., 2010. Oxidative stress caused by mitochondrial calcium overload. Annals of the New York Academy of Sciences 1201, 183-188. Petronilli, V., Penzo, D., Scorrano, L., Bernardi, P., Di Lisa, F., 2001. The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ. The Journal of biological chemistry 276, 12030-12034. Petrosillo, G., Moro, N., Ruggiero, F.M., Paradies, G., 2009. Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release. Free radical biology & medicine 47, 969-974. Petrosillo, G., Ruggiero, F.M., Paradies, G., 2003. Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17, 2202-2208. Petrosillo, G., Ruggiero, F.M., Pistolese, M., Paradies, G., 2001. Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation. Possible role in the apoptosis. FEBS letters 509, 435-438. Pramanik, K.C., Boreddy, S.R., Srivastava, S.K., 2011. Role of mitochondrial electron transport chain complexes in capsaicin mediated oxidative stress leading to apoptosis in pancreatic cancer cells. PloS one 6, e20151. Risso, A., Braidot, E., Sordano, M.C., Vianello, A., Macri, F., Skerlavaj, B., Zanetti, M., Gennaro, R., Bernardi, P., 2002. BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore. Molecular and cellular biology 22, 1926-1935. Rodriguez de Fonseca, F., Del Arco, I., Bermudez-Silva, F.J., Bilbao, A., Cippitelli, A., Navarro, M., 2005. The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol 40, 2-14. Sacerdote, P., Martucci, C., Vaccani, A., Bariselli, F., Panerai, A.E., Colombo, A., Parolaro, D., Massi, P., 2005. The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitro. Journal of neuroimmunology 159, 97-105. Subramanian, R.R., Masters, S.C., Zhang, H., Fu, H., 2001. Functional conservation of 14-3-3 isoforms in inhibiting bad-induced apoptosis. Experimental cell research 271, 142-151. Tait, S.W., Green, D.R., 2010. Mitochondria and cell death: outer membrane permeabilization and beyond. Nature reviews. Molecular cell biology 11, 621-632. Turrens, J.F., 2003. Mitochondrial formation of reactive oxygen species. The Journal of physiology 552, 335-344. Wang, C.C., Liu, T.Y., Cheng, C.H., Jan, T.R., 2009. Involvement of the mitochondrion-dependent pathway and oxidative stress in the apoptosis of murine splenocytes induced by areca nut extract. Toxicology in vitro : an international journal published in association with BIBRA 23, 840-847. Wang, H.G., Pathan, N., Ethell, I.M., Krajewski, S., Yamaguchi, Y., Shibasaki, F., McKeon, F., Bobo, T., Franke, T.F., Reed, J.C., 1999. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 284, 339-343. Weiss, L., Zeira, M., Reich, S., Har-Noy, M., Mechoulam, R., Slavin, S., Gallily, R., 2006. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39, 143-151. Williamson, E.M., Evans, F.J., 2000. Cannabinoids in clinical practice. Drugs 60, 1303-1314. Wright, S., 2007. Cannabinoid-based medicines for neurological disorders--clinical evidence. Molecular neurobiology 36, 129-136. Wu, H.Y., Chang, A.C., Wang, C.C., Kuo, F.H., Lee, C.Y., Liu, D.Z., Jan, T.R., 2010. Cannabidiol induced a contrasting pro-apoptotic effect between freshly isolated and precultured human monocytes. Toxicology and applied pharmacology. Wu, H.Y., Chu, R.M., Wang, C.C., Lee, C.Y., Lin, S.H., Jan, T.R., 2008. Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8. Toxicology and applied pharmacology 226, 260-270. Wu, H.Y., Goble, K., Mecha, M., Wang, C.C., Huang, C.H., Guaza, C., Jan, T.R., 2012. Cannabidiol-induced apoptosis in murine microglial cells through lipid raft. Glia 60, 1182-1190. Xiao, D., Powolny, A.A., Singh, S.V., 2008. Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. The Journal of biological chemistry 283, 30151-30163. Zhang, Y., Soboloff, J., Zhu, Z., Berger, S.A., 2006. Inhibition of Ca2+ influx is required for mitochondrial reactive oxygen species-induced endoplasmic reticulum Ca2+ depletion and cell death in leukemia cells. Molecular pharmacology 70, 1424-1434. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64936 | - |
| dc.description.abstract | 大麻二酚為一萃取自Cannabis sativa不具有中樞活性的天然生物鹼，具有抗發炎及免疫調節等藥理作用。目前已知大麻二酚對於多種癌化細胞及初代淋巴球、胸腺細胞以及單核球等具有促進凋亡的作用，且和氧化壓力有關。本研究目的為進一步探討大麻二酚造成人類單核球氧化性壓力以及引起細胞凋亡的機制。與先前報告結果一致，大麻二酚對於新鮮分離出的人類單核球具有凋亡效果，且具有時間與濃度相關性。時間相關性的實驗結果顯示，在給予大麻二酚後1-2小時會造成細胞內活性氧化物的增加。進一步比較後發現，在給予細胞大麻二酚5分鐘即造成粒線體膜電位去極化，且在15分鐘後造成粒線體內膜中心磷脂（cardiolipin）的氧化。大麻二酚也會造成粒線體中的細胞色素c（cytochrome c）釋放至細胞質，更加證明粒線體為大麻二酚的首要標的。除此之外，共軛膠顯微影像顯示，細胞內的氧化物螢光探針2’,7’-dichlorofluorescein與粒線體的螢光探針MitoTracker位置重和。流式細胞儀分析顯示，粒線體中鈣黃綠素（calcein）的螢光強度明顯減弱，證實大麻二酚會引起粒線體滲透性轉變。大麻二酚引起的凋亡和粒線體膜電位下降受到粒線體滲透性孔（mitochondrial permeability transition pore, MPTP）抑制劑環孢靈（cyclosporine A）的回復，但不受到鈣調去磷酸酶（calcineurin）抑制劑FK506的影響。另外，環孢靈也可抑制大麻二酚引起的粒線體心磷脂氧化和粒線體滲透性的轉變。綜合上述，大麻二酚引起人類周邊血液單核球的氧化性壓力和凋亡作用為粒線體所媒介，且為粒線體滲透性孔依賴性機制。 | zh_TW |
| dc.description.abstract | Cannabidiol (CBD), the major non-psychotropic cannabinoid contained in the plant Cannabis sativa, possesses a number of promising pharmacological activities, such as anti-inflammation and immunomodulation. CBD is known to induce apoptosis in both transformed and primary immune cells, including lymphocytes, thymocytes and monocytes, through oxidative stress-related mechanisms. The objective of this study was to investigate the underlying mechanisms for CBD-induced oxidative stress and apoptosis in monocytes. Consistent with previous results, exposure of freshly isolated human monocytes to CBD induced apoptosis in a time- and concentration-dependent manner. Time-course analyses revealed the induction of intracellular reactive oxygen species (ROS) at 1-2 h post CBD exposure. By comparison, CBD rapidly elicited the depolarization of mitochondrial membrane potential within 5 min, and the oxidation of cardiolipin, a major lipid component of the mitochondrial inner membrane, within 15 min of exposure. CBD also induced the release of cytochrome c from mitochondria to the cytosol, confirming that mitochondria are targeted by CBD. Furthermore, results from confocal microscopy demonstrated that the intracellular ROS measured by 2’,7’-dichlorofluorescein co-localized with the mitochondrial probe MitoTracker in CBD-treated monocytes. Flow cytometric analyses revealed that CBD induced the mitochondrial permeability transition (MPT) as evidenced by a marked decrease in the mitochondrial fluorescence of calcein. CBD-mediated apoptosis and mitochondrial depolarization were significantly attenuated in the presence of the mitochondrial permeability transition pore (MPTP pore) inhibitor cyclosporin A, but not affected by the calcineurin inhibitor FK506. Cyclosporin A also prevented cardiolipin oxidation and MPT induced by CBD. Taken together, the present study suggests that CBD may act at the level of mitochondria to initiate oxidative stress and apoptosis via MPTP-dependent mechanisms in human peripheral monocytes. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:08:59Z (GMT). No. of bitstreams: 1 ntu-101-R99629009-1.pdf: 1422326 bytes, checksum: b81808e3473ec75c0726d1e4d6eb9935 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract III Abbreviations V Contents VII Figures IX Chapter 1 Introduction 1 1.1 Cannabinoid background 1 1.2 Medicinal potential of cannabidiol (CBD) 2 1.3 Immunomodulatory and anti-inflammatory effects of CBD 4 1.4 Cannabidiol-induced apoptosis 5 1.5 Oxidative stress 6 1.6 Mitochondria and oxidative stress 8 1.7 Mitochondrial-mediated apoptosis 10 1.8 Mitochondrial permeability transition pore (MPTP) 12 Chapter 2 Materials and Methods 13 2.1 Chemicals and reagents 13 2.2 Cell cultures 15 2.3 Cell cycle analysis 16 2.4 Measurement of intracellular ROS 16 2.5 Measurement of mitochondrial membrane potential (MMP) and cardiolipin oxidation 17 2.6 Measurement of mitochondrial superoxide dismutase (SOD) activity 18 2.7 Measurement of mitochondrial permeability transition pore (MPTP) 19 2.8 Confocal microscopy 20 2.9 Western blotting 21 2.10 Statistical analysis 22 Chapter 3 Results 23 3.1 Cannabidiol (CBD) induced apoptosis in monocytes 23 3.2 CBD caused intracellular oxidative stress 23 3.3 CBD disrupted mitochondrial membrane potential (MMP) 24 3.4 CBD induced ROS production in mitochondria 24 3.5 CBD caused oxidation of cardiolipin 25 3.6 CBD induced the release of cytochrome c (Cyt c) from mitochondria 25 3.7 CBD treatment attenuated calcein fluorescence in mitochondria 26 3.8 Attenuation of CBD-induced MPT and apoptosis by MPTP inhibitors, but not by calcineurin inhibitor 26 3.9 No effect by CBD on the activity of mitochondrial superoxide dismutase (SOD) 27 3.10 CBD-induced mitochondrial ROS production was not affected by mitochondrial respiratory chain inhibitors. 27 3.11 CBD-induced apoptosis was not affected by deferoxamine (DFO), 1,2-bis(2aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and ruthenium red 28 Chapter 4 Discussion 43 References 48 | |
| dc.language.iso | zh-TW | |
| dc.title | 大麻二酚引起人類單核球氧化壓力與細胞凋亡之機制 | zh_TW |
| dc.title | The Mechanism of Cannabidiol-Mediated Oxidative Stress and Apoptosis in Human Monocytes
The Mechanism of Cannabidiol-Mediated Oxidative Stress and Apoptosis in Human Monocytes The Mechanism of Cannabidiol-Mediated Oxidative Stress and Apoptosis in Human Monocytes | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張芳嘉,李心予,李志恆,魏孝萍 | |
| dc.subject.keyword | 凋亡,大麻二酚,粒線體滲透性轉變,單核球,活性氧化物, | zh_TW |
| dc.subject.keyword | apoptosis,cannabidiol,mitochondrial permeability transition,monocyte,reactive oxygen species, | en |
| dc.relation.page | 58 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-06 | |
| dc.contributor.author-college | 獸醫專業學院 | zh_TW |
| dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
| 顯示於系所單位： | 獸醫學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 目前未授權公開取用 | 1.39 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。