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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Yen-Ting Tseng | en |
| dc.contributor.author | 曾彥婷 | zh_TW |
| dc.date.accessioned | 2021-06-08T02:29:06Z | - |
| dc.date.copyright | 2015-08-25 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-16 | |
| dc.identifier.citation | Beauvais, F., Michel, L., and Dubertret, L. (1995). Human eosinophils in culture undergo a striking and rapid shrinkage during apoptosis. Role of K+ channels. Journal of leukocyte biology 57, 851-855.
Benson, R.S., Heer, S., Dive, C., and Watson, A.J. (1996). Characterization of cell volume loss in CEM-C7A cells during dexamethasone-induced apoptosis. The American journal of physiology 270, C1190-1203. Bortner, C.D., and Cidlowski, J.A. (1999). Caspase independent/dependent regulation of K(+), cell shrinkage, and mitochondrial membrane potential during lymphocyte apoptosis. The Journal of biological chemistry 274, 21953-21962. Bortner, C.D., and Cidlowski, J.A. (2004). The role of apoptotic volume decrease and ionic homeostasis in the activation and repression of apoptosis. Pflugers Archiv : European journal of physiology 448, 313-318. Bortner, C.D., Hughes, F.M., Jr., and Cidlowski, J.A. (1997). A primary role for K+ and Na+ efflux in the activation of apoptosis. The Journal of biological chemistry 272, 32436-32442. Chen, F., Hersh, B.M., Conradt, B., Zhou, Z., Riemer, D., Gruenbaum, Y., and Horvitz, H.R. (2000). Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science 287, 1485-1489. Chen, Y.Z., Mapes, J., Lee, E.S., Skeen-Gaar, R.R., and Xue, D. (2013). Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization. Nature communications 4, 2726. Conradt, B., and Horvitz, H.R. (1998). The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93, 519-529. Doi, M., and Iwasaki, K. (2008). Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner. Molecular and cellular neurosciences 38, 548-558. Ellis, H.M., and Horvitz, H.R. (1986). Genetic control of programmed cell death in the nematode C. elegans. Cell 44, 817-829. Ellis, R.E., Jacobson, D.M., and Horvitz, H.R. (1991). Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. Genetics 129, 79-94. Erwig, L.P., and Henson, P.M. (2008). Clearance of apoptotic cells by phagocytes. Cell death and differentiation 15, 243-250. Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J., Bratton, D.L., and Henson, P.M. (1992). Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. Journal of immunology 148, 2207-2216. Gomez-Angelats, M., Bortner, C.D., and Cidlowski, J.A. (2000). Cell volume regulation in immune cell apoptosis. Cell and tissue research 301, 33-42. Govorunova, E.G., Moussaif, M., Kullyev, A., Nguyen, K.C., McDonald, T.V., Hall, D.H., and Sze, J.Y. (2010). A homolog of FHM2 is involved in modulation of excitatory neurotransmission by serotonin in C. elegans. PloS one 5, e10368. Hsu, T.Y., and Wu, Y.C. (2010). Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling. Current biology : CB 20, 477-486. Hughes, F.M., Jr., Bortner, C.D., Purdy, G.D., and Cidlowski, J.A. (1997). Intracellular K+ suppresses the activation of apoptosis in lymphocytes. The Journal of biological chemistry 272, 30567-30576. Hughes, F.M., Jr., and Cidlowski, J.A. (1998). Glucocorticoid-induced thymocyte apoptosis: protease-dependent activation of cell shrinkage and DNA degradation. The Journal of steroid biochemistry and molecular biology 65, 207-217. Kaplan, M., Summerfield, M.R., and Pestaner, J.P. (2002). Mix-up between potassium chloride and sodium polystyrene sulfonate. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 59, 1786-1787. Krahling, S., Callahan, M.K., Williamson, P., and Schlegel, R.A. (1999). Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages. Cell death and differentiation 6, 183-189. Lang, F., Busch, G.L., Ritter, M., Volkl, H., Waldegger, S., Gulbins, E., and Haussinger, D. (1998). Functional significance of cell volume regulatory mechanisms. Physiological reviews 78, 247-306. Lang, F., and Hoffmann, E.K. (2012). Role of ion transport in control of apoptotic cell death. Comprehensive Physiology 2, 2037-2061. Lettre, G., and Hengartner, M.O. (2006). Developmental apoptosis in C. elegans: a complex CEDnario. Nature reviews Molecular cell biology 7, 97-108. Liu, J., Dai, Q., Chen, J., Durrant, D., Freeman, A., Liu, T., Grossman, D., and Lee, R.M. (2003). Phospholipid scramblase 3 controls mitochondrial structure, function, and apoptotic response. Molecular cancer research : MCR 1, 892-902. Liu, J., Epand, R.F., Durrant, D., Grossman, D., Chi, N.W., Epand, R.M., and Lee, R.M. (2008). Role of phospholipid scramblase 3 in the regulation of tumor necrosis factor-alpha-induced apoptosis. Biochemistry 47, 4518-4529. Maeno, E., Ishizaki, Y., Kanaseki, T., Hazama, A., and Okada, Y. (2000). Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proceedings of the National Academy of Sciences of the United States of America 97, 9487-9492. Maghsoudi, N., Zakeri, Z., and Lockshin, R.A. (2012). Programmed cell death and apoptosis--where it came from and where it is going: from Elie Metchnikoff to the control of caspases. Experimental oncology 34, 146-152. Maurer, C.W., Chiorazzi, M., and Shaham, S. (2007). Timing of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene. Development 134, 1357-1368. Mello, C.C., Kramer, J.M., Stinchcomb, D., and Ambros, V. (1991). Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. The EMBO journal 10, 3959-3970. Mitani, S., Du, H., Hall, D.H., Driscoll, M., and Chalfie, M. (1993). Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans. Development 119, 773-783. Morth, J.P., Poulsen, H., Toustrup-Jensen, M.S., Schack, V.R., Egebjerg, J., Andersen, J.P., Vilsen, B., and Nissen, P. (2009). The structure of the Na+,K+-ATPase and mapping of isoform differences and disease-related mutations. Philosophical transactions of the Royal Society of London Series B, Biological sciences 364, 217-227. Okada, M. (2012). Regulation of the SRC family kinases by Csk. International journal of biological sciences 8, 1385-1397. Perez, G.I., Maravei, D.V., Trbovich, A.M., Cidlowski, J.A., Tilly, J.L., and Hughes, F.M., Jr. (2000). Identification of potassium-dependent and -independent components of the apoptotic machinery in mouse ovarian germ cells and granulosa cells. Biology of reproduction 63, 1358-1369. Qi, S., Pang, Y., Hu, Q., Liu, Q., Li, H., Zhou, Y., He, T., Liang, Q., Liu, Y., Yuan, X., et al. (2010). Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141, 446-457. Steller, H. (1995). Mechanisms and genes of cellular suicide. Science 267, 1445-1449. Sulston, J.E., and Horvitz, H.R. (1977). Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Developmental biology 56, 110-156. Tian, J., Cai, T., Yuan, Z., Wang, H., Liu, L., Haas, M., Maksimova, E., Huang, X.Y., and Xie, Z.J. (2006). Binding of Src to Na+/K+-ATPase forms a functional signaling complex. Molecular biology of the cell 17, 317-326. Xie, Z. (2003). Molecular mechanisms of Na/K-ATPase-mediated signal transduction. Annals of the New York Academy of Sciences 986, 497-503. Yurinskaya, V., Goryachaya, T., Guzhova, I., Moshkov, A., Rozanov, Y., Sakuta, G., Shirokova, A., Shumilina, E., Vassilieva, I., Lang, F., et al. (2005a). Potassium and sodium balance in U937 cells during apoptosis with and without cell shrinkage. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16, 155-162. Yurinskaya, V.E., Moshkov, A.V., Rozanov, Y.M., Shirokova, A.V., Vassilieva, I.O., Shumilina, E.V., Lang, F., Volgareva, E.V., and Vereninov, A.A. (2005b). Thymocyte K+, Na+ and water balance during dexamethasone- and etoposide-induced apoptosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16, 15-22. Zakeri, Z., Lockshin, R.A., and Martinez, A.C. (2001). Meeting report: mechanisms of cell death 2000. Apoptosis : an international journal on programmed cell death 6, 403-404. Zhang, Y., Wang, H., Kage-Nakadai, E., Mitani, S., and Wang, X. (2012). C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment. Current biology : CB 22, 1276-1284. Zhou, Q., Zhao, J., Wiedmer, T., and Sims, P.J. (2002). Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1. Blood 99, 4030-4038. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19951 | - |
| dc.description.abstract | 計畫性細胞凋亡的主要功能為清除個體中多餘的細胞並維持個體一定的細胞數，對於個體的成長及發育扮演極為重要的角色。細胞凋亡的過程主要可以分為：辨認死細胞、執行死亡、吞噬以及分解等四個步驟。在執行死亡的步驟進行過後，死細胞還會發生磷脂絲氨酸(phosphatidylserine/PS)外翻到細胞膜、細胞型態改變，以及DNA 斷裂降解等現象。過去的研究中發現在線蟲中調控細胞凋亡的基因有數十種，而其中執行死亡的步驟主要是由EGL-1(a BH3-containing protein)，CED-9(Bcl-2)，CED-4(Apaf-1)以及CED-3(Caspase)所調控；然而這四者又是如何被其他基因所調控仍有待研究。本實驗室在過去研究中發現，在eat-6 這個鈉鉀ATP 酶α 次單元異變種胚胎中，細胞屍體(cell corpse)數目有下降的趨勢。本篇論文主要探討EAT-6 是如何造成死細胞數目降低，而我利用死細胞的磷脂絲氨酸會外翻到細胞膜外並與分泌型的Annexin V 結合形成環狀外觀的特性進行分析。實驗結果指出eat-6 的異變種中，沒有死細胞型態但卻會與Annexin V 結合所形成環狀型態有增加的趨勢，這表示eat-6 會影響到死亡細胞型態的形成和脂絲氨酸的外翻。我的遺傳實驗結果也發現，eat-6 會與csk-1 這個非受體性酪氨酸磷酸酶一同參與在核心路徑中去調控細胞凋亡。而另一方面我也發現過度表現EAT-6 則會促進接觸性神經(touch neuron)的細胞凋亡，且eat-6 會作用在egl-1 的上游去促進細胞凋亡的功能且此種功能是需要其運輸離子的功能。以上實驗結果指出eat-6 除了擁有運送鈉鉀離子維持膜電位的功能外，也會影響到死細胞的屍體型態及其脂絲氨酸的外翻。
關鍵字：線蟲、計畫性細胞凋亡、鈉鈉鉀ATP 酶、細胞屍體、外觀型態變、脂絲 氨酸外翻 | zh_TW |
| dc.description.abstract | Programmed cell death (PCD) is important for development and homeostasis of multicellular organisms. The PCD process occurs via four steps: decision, execution,engulfment, and degradation. After execution step, the dying cells proceed phosphatidylserine (PS) translocation, refractile cell corpse morphology formation and DNA degradation during apoptosis. Previous studies have identified and characterized about 28 genes that regulate the PCD process in Caenorhabditis elegans. Among these genes, egl-l (encoding BH3-containing protein), ced-9 (Bcl-2), ced-4 (Apaf-1) and ced-3(Caspase) act in an inhibitory cascade to activate PCD. Our previous data have reported that loss of eat-6, which encodes the alpha subunit of sodium/potassium ion channel,results in significant reduction of cell corpses in the embryos. My studies are focused on how eat-6 affect the number of cell corpses. During apoptosis, the phosphatidylserine (PS)located in the inner leaflet of the plasma membrane is exposed on the surface of apoptotic cells. I used secreted Annexin V fusion GFP as a PS sensor to detect the dying cells. The results showed that Annexin V binding normally to the cell corpses in eat-6 mutant. However, the eat-6 mutant has more extra Annexin V-PS binding rings around the dying cells without cell corpse morphology than the wild type embryos. These results indicated that eat-6 may impact the formation of refractile cell corpse morphology and the translocation of PS. My genetic analysis also showed that eat-6 may work with csk-1, a non-receptor tyrosine kinase to promote cell death. In addition, overexpression of eat-6 can act upstream or in parallel to egl-1 to kill touch neurons and this killing function isdependent on its ATPase activity which is required for pumping. According to these data,eat-6 functions not only in maintaining membrane potential but also in affecting the morphology formation and PS translocation of dying cells.
Keywords: C. elegans, programmed cell death, Na+-K+ ATPase, cell corpse, morphology change, phosphatidylserine (PS) translocation | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T02:29:06Z (GMT). No. of bitstreams: 1 ntu-104-R02b43013-1.pdf: 1341046 bytes, checksum: 62471c9be0f30df49e9b1d36d98f11bb (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | Table of contents
論文口試委員審定書....................................................................................................... i 致謝 .................................................................................................................................. ii 中文摘要 ...........................................................................................................................I Abstract ......................................................................................................................... III Introduction .................................................................................................................... 1 Material and Methods .................................................................................................... 5 Strains and alleles ......................................................................................................... 5 Transgenic animals ....................................................................................................... 6 RNAi experiments ........................................................................................................ 6 Four-dimensional microscopy analysis of the first 13 cells death in the AB cell lineage ........................................................................................................................... 7 Annexin V binding assay .............................................................................................. 7 Extra cell analysis ......................................................................................................... 8 Sterile phenotype and lethality of progeny analysis ..................................................... 8 Results .............................................................................................................................. 8 1. Mutations of eat-6 reduces cell corpses during embryogenesis. ..................... 8 2. The mutation in eat-6 likely do not result in survival of cells that destined to die 9 3. Mutation in eat-6 cannot suppress the phenotype of ced-9 ........................... 11 4. The mutation of eat-6 does not enhance the cell corpses engulfing process during embryogenesis ............................................................................................... 12 5. The mutation of eat-6 affects cell corpse morphology formation and PS translocation .............................................................................................................. 13 6. eat-6 acts in the same pathway with csk-1 to affect cell corpse number during embryogenesis ............................................................................................... 14 7. Overexpression of eat-6 causes ectopic cell death .......................................... 16 8. Ion pumping activity of eat-6 is important for its killing activity ................ 16 9. eat-6 may acts upstream of or in parallel to egl-1 to promote PCD ............. 16 Discussion ...................................................................................................................... 17 Reference ....................................................................................................................... 22 Tables and figures ......................................................................................................... 29 Table 1. Mutation in eat-6 causes decreased cell corpses phenotype ......................... 29 Table 2. The first 13 cell death in the AB lineage die normally in the eat-6 mutant . 30 Table 3. eat-6 acts in the same pathway with csk-1 to affect embryonic cell corpse numbers at the 2-fold stage ......................................................................................... 31 Table 4. eat-6 cannot suppress the sterile phenotype or lethality of the ced-9(lf) mutant ......................................................................................................................... 31 Table 5. eat-6 acts cell-autonomously to kill touch neurons ...................................... 32 Table 6. Ion pumping activity of eat-6 is important for its killing activity ................ 32 Figure 1. The genes involved in the programmed cell death ...................................... 33 Figure 2. Schematic representation of EAT-6 ............................................................ 34 Figure 3. There are no extra sister cells of I1 neurons in eat-6(ad997) mutant .......... 35 Figure 4. There are no extra sister cells of RIA neurons in eat-6(ad997) mutant ...... 36 Figure 5. There are no extra sister cells of M4 cells in eat-6(ad997) mutant ............. 37 Figure 6. A mutation of eat-6 partially affects cell corpse morphology and PS translocation ................................................................................................................ 39 Figure 7. Overexpression of egl-1 can kill most touch neurons in eat-6 mutant ........ 40 Figure 8. The proposed model for the regulation mechanism of eat-6 during apoptosis .................................................................................................................................... 41 Supplementary data ..................................................................................................... 42 Table S1. Overexpression of csk-1 rescued the apoptotic defect in eat-6 mutant ...... 42 Table S2. csk-1 mediates programmed cell death in a ced-3 and ced-4-dependent manner ........................................................................................................................ 43 Table S3. Loss of eat-6 does not result in extra surviving cells in the pharynx ......... 44 Table S4. Pumping activity of EAT-6 not participate in programmed cell death ...... 45 Table S5. Overexpression of eat-6 cannot kill cells in the absence of egl-1 or ced-4 46 Figure S1. The duration time of eat-6 mutant wild type animals is almost the same . 47 Figure S2. The β subunit nkb-1, nkb-2 and nkb-3 mutations do not affect cell corpse numbers during embryogenesis .................................................................................. 48 Figure S3. EAT-6 physically interacts with CSK-1 in vitro and is co-localized with CSK-1 on the surface of apoptotic cells in vivo .......................................................... 49 | |
| dc.language.iso | en | |
| dc.title | 鈉鉀ATP酶α次單元EAT-6調控線蟲計劃性細胞凋
亡中細胞外觀變化和磷脂絲氨酸的外翻 | zh_TW |
| dc.title | The alpha subunit of Na+/K+ ATPase/EAT-6
is involved in morphological changes and phosphatidylserine exposure during apoptosis in C. elegans | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳瑞菁(Jui-Ching Wu),陳俊宏(Chun-Hong Chen) | |
| dc.subject.keyword | 線蟲,計畫性細胞凋亡,鈉鈉鉀ATP ?,細胞屍體,外觀型態變,脂絲氨酸外翻, | zh_TW |
| dc.subject.keyword | C. elegans,programmed cell death,Na+-K+ ATPase,cell corpse,morphology change,phosphatidylserine (PS) translocation, | en |
| dc.relation.page | 49 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-08-16 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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