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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 柯逢春 | |
| dc.contributor.author | Meng-Jen Tsai | en |
| dc.contributor.author | 蔡孟真 | zh_TW |
| dc.date.accessioned | 2021-06-15T02:48:49Z | - |
| dc.date.available | 2009-08-12 | |
| dc.date.copyright | 2009-08-12 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-06 | |
| dc.identifier.citation | [ ] Warburg, O. (1925). Uber den Stoffwechsel der Carcinomzelle. Klin. Wochenschr. 4, 534–536.
[ ] DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., and Thompson, C. B. (2008). The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7, 11-20. [ ] Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A., and Thompson, C. B. (2005). ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8, 311-321. [ ] Guppy, M., Greiner, E., and Brand, K. (1993). The role of the Crabtree effect and an endogenous fuel in the energy metabolism of resting and proliferating thymocytes. Eur J Biochem 212, 95-99. [ ] Curi, R., Newsholme, P., and Newsholme, E. A. (1988). Metabolism of pyruvate by isolated rat mesenteric lymphocytes, lymphocyte mitochondria and isolated mouse macrophages. Biochem J 250, 383-388. [ ] Portais, J. C., Voisin, P., Merle, M., and Canioni, P. (1996). Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR. Biochimie 78, 155-164. [ ] DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., and Thompson, C. B. (2007). Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 104, 19345-19350. [ ] Wullschleger, S., Loewith, R., and Hall, M. N. (2006). TOR signaling in growth and metabolism. Cell 124, 471-484. [ ] Kim, D. H., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2002). mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-175. [ ] Kim, D. H., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K. V., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2003). GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11, 895-904. [ ] Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., and Hall, M. N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10, 457-468. [ ] Bhaskar, P. T., and Hay, N. (2007). The two TORCs and Akt. Dev Cell 12, 487-502. [ ] Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., and Sabatini, D. M. (2006). Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 11, 859-871. [ ] Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., and Avruch, J. (2005). Rheb binds and regulates the mTOR kinase. Curr Biol 15, 702-713. [ ] Li, Y., Corradetti, M. N., Inoki, K., and Guan, K. L. (2004). TSC2: filling the GAP in the mTOR signaling pathway. Trends Biochem Sci 29, 32-38. [ ] Hay, N., and Sonenberg, N. (2004). Upstream and downstream of mTOR. Genes Dev 18, 1926-1945. [ ] Tee, A. R., and Blenis, J. (2005). mTOR, translational control and human disease. Semin Cell Dev Biol 16, 29-37. [ ] Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Ruegg, M. A., Hall, A., and Hall, M. N. (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6, 1122-1128. [ ] Sarbassov, D. D., Ali, S. M., Kim, D. H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D. M. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14, 1296-1302. [ ] Sarbassov, D. D., Guertin, D. A., Ali, S. M., and Sabatini, D. M. (2005). Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101. [ ] Lee, S., Comer, F. I., Sasaki, A., McLeod, I. X., Duong, Y., Okumura, K., Yates, J. R., 3rd, Parent, C. A., and Firtel, R. A. (2005). TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium. Mol Biol Cell 16, 4572-4583. [ ] Barata, J. T., Silva, A., Brandao, J. G., Nadler, L. M., Cardoso, A. A., and Boussiotis, V. A. (2004). Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells. J Exp Med 200, 659-669. [ ] Edinger, A. L., and Thompson, C. B. (2002). Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 13, 2276-2288. [ ] Wieman, H. L., Wofford, J. A., and Rathmell, J. C. (2007). Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell 18, 1437-1446. [ ] Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M., and Thompson, C. B. (2004). Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64, 3892-3899. [ ] Xu, R. H., Pelicano, H., Zhang, H., Giles, F. J., Keating, M. J., and Huang, P. (2005). Synergistic effect of targeting mTOR by rapamycin and depleting ATP by inhibition of glycolysis in lymphoma and leukemia cells. Leukemia 19, 2153-2158. [ ] Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., and Thompson, C. B. (2005). ATP citrate lyase is an important component of cell growth and transformation. Oncogene 24, 6314-6322. [ ] Barbet, N. C., Schneider, U., Helliwell, S. B., Stansfield, I., Tuite, M. F., and Hall, M. N. (1996). TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell 7, 25-42. [ ] Crespo, J. L., Powers, T., Fowler, B., and Hall, M. N. (2002). The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. Proc Natl Acad Sci U S A 99, 6784-6789. [ ] Drummond, M. J., and Rasmussen, B. B. (2008). Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care 11, 222-226. [ ] Hara, K., Yonezawa, K., Weng, Q. P., Kozlowski, M. T., Belham, C., and Avruch, J. (1998). Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 273, 14484-14494. [ ] Long, X., Ortiz-Vega, S., Lin, Y., and Avruch, J. (2005). Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem 280, 23433-23436. [ ] Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., and Chen, J. (2001). Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942-1945. [ ] Bai, X., Ma, D., Liu, A., Shen, X., Wang, Q. J., Liu, Y., and Jiang, Y. (2007). Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38. Science 318, 977-980. [ ] Byfield, M. P., Murray, J. T., and Backer, J. M. (2005). hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem 280, 33076-33082. [ ] Gulati, P., Gaspers, L. D., Dann, S. G., Joaquin, M., Nobukuni, T., Natt, F., Kozma, S. C., Thomas, A. P., and Thomas, G. (2008). Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34. Cell Metab 7, 456-465. [ ] Juhasz, G., Hill, J. H., Yan, Y., Sass, M., Baehrecke, E. H., Backer, J. M., and Neufeld, T. P. (2008). The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol 181, 655-666. [ ] Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., and Guan, K. L. (2008). Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 10, 935-945. [ ] Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., and Sabatini, D. M. (2008). The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496-1501. [ ] Findlay, G. M., Yan, L., Procter, J., Mieulet, V., and Lamb, R. F. (2007). A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J 403, 13-20. [ ] Cota, D., Proulx, K., Smith, K. A., Kozma, S. C., Thomas, G., Woods, S. C., and Seeley, R. J. (2006). Hypothalamic mTOR signaling regulates food intake. Science 312, 927-930. [ ] Shigemitsu, K., Tsujishita, Y., Miyake, H., Hidayat, S., Tanaka, N., Hara, K., and Yonezawa, K. (1999). Structural requirement of leucine for activation of p70 S6 kinase. FEBS Lett 447, 303-306. [ ] Xu, G., Kwon, G., Cruz, W. S., Marshall, C. A., and McDaniel, M. L. (2001). Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells. Diabetes 50, 353-360. [ ] Eto, K., Tsubamoto, Y., Terauchi, Y., Sugiyama, T., Kishimoto, T., Takahashi, N., Yamauchi, N., Kubota, N., Murayama, S., Aizawa, T., et al. (1999). Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science 283, 981-985. [ ] Hutson, S. M., Fenstermacher, D., and Mahar, C. (1988). Role of mitochondrial transamination in branched chain amino acid metabolism. J Biol Chem 263, 3618-3625. [ ] Schieke, S. M., Phillips, D., McCoy, J. P., Jr., Aponte, A. M., Shen, R. F., Balaban, R. S., and Finkel, T. (2006). The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 281, 27643-27652. [ ] Ruggero, D., Montanaro, L., Ma, L., Xu, W., Londei, P., Cordon-Cardo, C., and Pandolfi, P. P. (2004). The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med 10, 484-486. [ ] Dekanty, A., Lavista-Llanos, S., Irisarri, M., Oldham, S., and Wappner, P. (2005). The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-alpha/Sima. J Cell Sci 118, 5431-5441. [ ] Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., and Semenza, G. L. (2007). HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11, 407-420. [ ] Gordan, J. D., Thompson, C. B., and Simon, M. C. (2007). HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 12, 108-113. [ ] Teng CH., Ke FC. (2004). Cellular senescence induced by malate-asparate shuttle in human fibroblast WI38. Master Thesis, Institute of molecular and cellular biology, National Taiwan University. [51] Hayflick, L. (1965). The Limited In Vitro Lifetime Of Human Diploid Cell Strains. Exp Cell Res 37, 614-636. [ ] Mathon, N. F., Malcolm, D. S., Harrisingh, M. C., Cheng, L., and Lloyd, A. C. (2001). Lack of replicative senescence in normal rodent glia. Science 291, 872-875. [ ] Roninson, I. B. (2003). Tumor cell senescence in cancer treatment. Cancer Res 63, 2705-2715. [ ] Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., and Lowe, S. W. (1997). Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593-602. [ ] Narita, M., Nunez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., and Lowe, S. W. (2003). Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113, 703-716. [ ] Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., and et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92, 9363-9367. [ ] Itahana, K., Campisi, J., and Dimri, G. P. (2004). Mechanisms of cellular senescence in human and mouse cells. Biogerontology 5, 1-10. [ ] Lee CS., Ke FC. (2005). The inducible senescence mechanism of human fibroblast WI38 by transaminase inhibitor aminooxyacetic acid. Master Thesis, Institute of molecular and cell biology, National Taiwan University. [ ] Fan JJ., Ke FC. (2008). Involvement of mTORCs in premature cell senescence induced by aminooxyacetate inhibition of mitochondrial malate-aspartate shuttle. Master Thesis, Institute of molecular and cellular biology, National Taiwan University. [ ] Aledo, J. C. (2004). Glutamine breakdown in rapidly dividing cells: waste or investment? Bioessays 26, 778-785. [ ] Rimaniol, A. C., Mialocq, P., Clayette, P., Dormont, D., and Gras, G. (2001). Role of glutamate transporters in the regulation of glutathione levels in human macrophages. Am J Physiol Cell Physiol 281, C1964-1970. [ ] Hyde, R., Taylor, P. M., and Hundal, H. S. (2003). Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem J 373, 1-18. [ ] Aledo, J. C., Segura, J. A., Medina, M. A., Alonso, F. J., Nunez de Castro, I., and Marquez, J. (1994). Phosphate-activated glutaminase expression during tumor development. FEBS Lett 341, 39-42. [ ] Forbes, N. S., Meadows, A. L., Clark, D. S., and Blanch, H. W. (2006). Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis. Metab Eng 8, 639-652. [ ] Brand, K. (1985). Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. Biochem J 228, 353-361. [ ] Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R., and Lazebnik, Y. (2007). Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 178, 93-105. [ ] Gomez-Fabre, P. M., Aledo, J. C., Del Castillo-Olivares, A., Alonso, F. J., Nunez De Castro, I., Campos, J. A., and Marquez, J. (2000). Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase. Biochem J 345 Pt 2, 365-375. [ ] Curthoys, N. P., and Watford, M. (1995). Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 15, 133-159. [ ] Richards, N. G., and Kilberg, M. S. (2006). Asparagine synthetase chemotherapy. Annu Rev Biochem 75, 629-654. [ ] Lorenzi, P. L., Llamas, J., Gunsior, M., Ozbun, L., Reinhold, W. C., Varma, S., Ji, H., Kim, H., Hutchinson, A. A., Kohn, E. C., et al. (2008). Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines. Mol Cancer Ther 7, 3123-3128. [ ] Rej, R. (1977). Aminooxyacetate is not an adequate differential inhibitor of aspartate aminotransferase isoenzymes. Clin Chem 23, 1508-1509. [ ] Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., and Puigserver, P. (2007). mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 450, 736-740. [ ] Newton, A. C. (2003). Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J 370, 361-371. [ ] Hietakangas, V., and Cohen, S. M. (2007). Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev 21, 632-637. [ ] Hresko, R. C., and Mueckler, M. (2005). mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. J Biol Chem 280, 40406-40416. [ ] Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A., Gould, C., Lowry, C., Newton, A. C., Mao, Y., Miao, R. Q., et al. (2008). The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. Embo J 27, 1932-1943. [ ] Ikenoue, T., Inoki, K., Yang, Q., Zhou, X., and Guan, K. L. (2008). Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. Embo J 27, 1919-1931. [ ] Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., and Thomas, G. (2001). Mammalian TOR: a homeostatic ATP sensor. Science 294, 1102-1105. [ ] Soubannier, V., and McBride, H. M. (2009). Positioning mitochondrial plasticity within cellular signaling cascades. Biochim Biophys Acta 1793, 154-170. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44282 | - |
| dc.description.abstract | 粒線體在細胞生長(cell growth)上扮演重要角色，當細胞進入生長、增生狀
態時，必須進行以粒線體角色轉換為主軸的代謝重整(metabolic reprogramming)： 粒線體TCA cycle將其中間產物輸出，提供生長所需之巨分子合成的材料，此即 為cataplerosis 作用。而細胞生長所需的大量ATP 則轉由glycolysis 提供，並提高 LDH-A活性，將pyruvate快速轉換為lactate排出，同時維持細胞質NAD+/NADH ratio，確保glycolysis 的進行。同時，細胞必須補充流失的TCA cycle 中間產物， 此即為補充效應(anaplerosis)，它給予細胞使用TCA cycle的中間產物作為生合成 所需前驅物的能力，是細胞生長的重要特徵。其中，胺基酸glutamine 的代謝為 一anaplerosis 的重要來源，可被glutaminase 轉成glutamate，再經由GDH 轉成 aKG，而進入TCA cycle進行補充。 在人類纖維母細胞WI38 中，處理粒線體malate-aspartate shuttle 的抑制物 AOA，會造成細胞停止增生、細胞老化(senescence)，以及mTORC1 活性下降， 而mTORC2 活性上升的現象。此些AOA 處理所引發的效應，會在與aKG 或 NEAA 共同處理之下而受到阻礙。我們推論aKG 是藉由anaplerosis 補充TCA cycle，而反轉AOA 所造成的效應。而NEAA 是七種非必需氨基酸的混合物， 逐一測試其中成分之後，發現唯有aspartate與aspargine有阻礙AOA 的效果，以 aspartate效果最好。Aspartate的作用可能是透過競爭性抑制而弱化AOA的效果， 或是透過提升asparagine synthetase 活性而產生作用。此外，leucine 是促進 mTORC1 活性效果最明顯的胺基酸，又mTORC1 與粒線體活性間互有影響關 係，但實驗發現leucine沒有反轉AOA的效果。 本研究透過在aKG 或aspartate 添加之下可阻斷AOA 所誘發的細胞停止增 生及老化的效應顯示，粒線體malate-aspartate shuttle活性為細胞增長所必須，可 能在anaplerosis 中扮演重要角色，突顯出粒線體功能轉換之代謝重整(metabolic reprogramming)在細胞生長過程中的重要性。 | zh_TW |
| dc.description.abstract | Mitochondria play a crucial role in cell growth. The switching role of
mitochondria TCA cycle from producing maximal amount of ATP to exporting much of the intermediates for lipid, protein, and nucleic acid synthesis is the main part of “metabolic reprogramming” process that necessary for cells to proliferate. This results in a continuous efflux of intermediates, which is so-called cataplerosis. In response to cataplerosis, cells switch the generation of ATP from TCA cycle to glycolysis and enhance LDH-A activity to convert pyruvate into lactate and also maintain the NAD+/NADH ratio, ensuring high glycolytic flux in proliferating cells. In order to sustain TCA cycle function under cataplerosis, cells must re-supply TCA cycle intermediates, which is so-called anaplerosis. Anaplerosis is critical for cell growth because it enables cells to use TCA cycle as a supply of biosynthetic precursors. Glutamine metabolism is one of the anaplerotic sources. Proliferating cells metabolize glutamine into glutamate and then aKG, which is convenient for cells to use as carbon source for TCA cycle, providing anaplerosis sources in growing cells. In WI38 cells system, the malate-aspartate shuttle inhibitor, AOA, induces cell cycle arrest and senescence with the reduction of mTORC1 and promotion of mTORC2 activity. These effects are blocked by co-treating aKG or NEAA. The reversal effect of aKG on AOA treatment is believed as replenishing TCA cycle intermediates through anaplerosis pathway. On the other hand, after testing individual amino acid in NEAA, we discovered that only aspartate and asparagine can rescue the cell cycle arrest and senescence ratio caused by AOA and the effect of aspartate is better than asparagine. Aspartate may function through enhancing asparagine synthetase activity or as a competitor of AOA thus attenuating its effect. We also tried leucine because of its greatest effect on activating mTORC1. However, addition of leucine has no effect to reverse AOA-induced cell cycle arrest and senescence. iv In this study, we found that the function of malate-aspartate shuttle is important for cell growth, implying that malate-aspartate shuttle is essential in anaplerosis. This study also points out the importance of mitochondria switching role in metabolic reprogramming in cell growth. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T02:48:49Z (GMT). No. of bitstreams: 1 ntu-98-R95b43021-1.pdf: 1015647 bytes, checksum: 61e2b2ac821a921a72ae1514a6b0808a (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 誌謝 i
摘要 ii Abstract iii 目錄 v 圖目錄 vii 檢索表 viii 引言 1 粒線體(mitochondria)在細胞生長(cell growth)所扮演的角色 1 細胞生長(cell growth)的中心調節者: mTOR 3 胺基酸(amino acid)調控mTORC1的活性 6 實驗目的 12 材料與方法 14 材料 14 細胞培養 14 生長曲線 15 老化比例測定(Senescence Associated β-galatosidase stain) 15 結果 17 NEAA可以阻礙AOA造成的cell cycle arrest以及senescence 17 NEAA若去除aspartate和asparagine則失去反轉AOA所引發之cell cycle arrest和senescence的能力 18 Aspartate以及asparagine有效阻礙AOA所引發的cell cycle arrest和senescence 19 Aspartate透過其transporter運送至細胞內 19 Leucine不能反轉由AOA引起的cell cycle arrest和senescence 21 討論 22 參考文獻 37-46 | |
| dc.language.iso | zh-TW | |
| dc.subject | 細胞老化 | zh_TW |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 代謝重整 | zh_TW |
| dc.subject | AOA | zh_TW |
| dc.subject | malate-aspartate shuttle | zh_TW |
| dc.subject | mitochondria | en |
| dc.subject | AOA | en |
| dc.subject | metabolic reprogramming | en |
| dc.subject | cell growth | en |
| dc.subject | malate-aspartate shuttle | en |
| dc.title | 胺基酸對Aminooxyacetate所引發之早發性細胞老化的抑制作用探討 | zh_TW |
| dc.title | The Reversal Effect of Amino Acids on Aminooxyacetate-induced Cellular Senescence | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李明亭,黃火煉,黃娟娟,蕭培文 | |
| dc.subject.keyword | 粒線體,代謝重整,AOA,malate-aspartate shuttle,細胞老化, | zh_TW |
| dc.subject.keyword | AOA,malate-aspartate shuttle,mitochondria,cell growth,metabolic reprogramming, | en |
| dc.relation.page | 46 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-08-06 | |
| 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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