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研究生:李婉瑜
研究生(外文):Wan-Yu Lee
論文名稱:老年人之皮膚纖維母細胞中有氧至無氧代謝轉換之研究
論文名稱(外文):Aerobic-to-Anaerobic Metabolic Shift in Human Skin Fibroblasts from Elderly Subjects
指導教授:魏耀揮魏耀揮引用關係
指導教授(外文):Yau-Huei Wei
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:69
中文關鍵詞:老化初代皮膚纖維母細胞粒線體活性氧分子葡萄糖代謝
外文關鍵詞:agingprimary skin fibroblastsmitochondriaROSglucose metabolism
相關次數:
  • 被引用被引用:1
  • 點閱點閱:244
  • 評分評分:
  • 下載下載:70
  • 收藏至我的研究室書目清單書目收藏:0
老化是近年來越來越受科學家注目之多因素影響的複雜過程,目前已有許多研究指出,在老化的過程中會逐漸出現粒線體功能缺失、活性氧分子的生成與累積以及相關基因的改變。我們認為在細胞逐漸衰老的過程中,葡萄糖的代謝會從原本由有氧呼吸產生能量,轉變成較為依賴無氧糖解來進行代謝。在此研究中,我們利用不同年紀捐贈者之皮膚組織培養出來的初代皮膚纖維母細胞當做實驗材料,並分析粒線體相關表現與功能上的改變。實驗結果發現從較年長的捐贈者身上所培養出來的皮膚纖維母細胞的增生時間較長、細胞的形態較為平坦、且受到��-gal染色的比例較高,顯示其的確有較為衰老的現象。同時,在老年組的細胞中,其電子傳遞鏈中Complex I的次單元之表現量有明顯的下降,且其在有氧呼吸作用中的氧化磷酸化效率也較差,此外,粒線體內的活性氧分子的含量也有上升的現象,伴隨著抗氧化酵素的表現有不平衡的情況。另外一方面,葡萄糖的攝取及乳酸的產生速率在老化的細胞中都有較快的情況,同時伴隨著無氧糖解部分酵素的表現量及活性的上昇。綜合以上結果,我發現在老化的過程中,葡萄糖會從依賴有氧呼吸的代謝,轉變成較為依賴無氧糖解來進行代謝,而這樣代謝路徑的轉移也許和老化的過程中粒線體的缺陷有關,但是此種代謝轉移的詳細調控機制仍有待進一步的探討。這裡所發現的結果也許能夠幫助我們更深入的了解在老化的過程中,細胞於生理及病理上所發生的改變,以期能了解老化與其相關疾病的發生原因,並從中發展出有效的預防與治療之方法。
Aging is a multi-factorial process that has received increasing attention of biomedical researchers in recent years. It has been reported that mitochondrial function decline, increased production of reactive oxygen species (ROS) and altered gene expression are associated with aging. We have hypothesized that metabolism is shifted from aerobic respiration to anaerobic glycolysis when human cells become progressively senescent. In this study, we established primary cultures of skin fibroblasts from donors of different ages. The mitochondria-related alterations were assessed at the molecular and cellular biology levels. The results showed that the cells from elderly subjects were more senescent and characterized by longer doubling time, flattened cell morphology, and higher proportion of ��-galactosidase-positive cells. Moreover, there was a significant decrease in the expression of subunits of Complex I and the respiration was low efficiency of oxidative phosphorylation in skin fibroblasts from elderly subjects. In addition, the intracellular level of ROS increased concurrently with an imbalanced expression of antioxidant enzymes. On the other hand, glucose uptake and lactate production were both increased concurrently with an up-regulation of glycolytic enzymes in skin fibroblasts from old donors. Taken together, we demonstrated that a metabolic shift from aerobic respiration to anaerobic glycolysis occurs as a compensation for mitochondrial dysfunction during aging. The findings of this study help us gain a deeper understanding of the metabolic changes of senescent cells at the molecular and cellular levels.
目錄

中文摘要………………………………………………2
英文摘要………………………………………………3
縮寫表…………………………………………………4
緒論……………………………………………………6
實驗材料與方法………………………………………16
實驗結果………………………………………………28
討論……………………………………………………34
參考文獻………………………………………………42
圖與表……………………………………………........51
1. Hayflick, L. (1998) How and why we age. Exp Gerontol 33, 639-653.
2. Harman, D. (2006) Free radical theory of aging: an update: increasing the functional life span. Ann NY Acad Sci 1067, 10-21.
3. Hiona, A. & Leeuwenburgh, C. (2008) The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol 43, 24-33.
4. Wei, Y.H., Ma, Y.S., Lee, H.C., Lee, C.F. & Lu, C.Y. (2001) Mitochondrial theory of aging matures--roles of mtDNA mutation and oxidative stress in human aging. Zhonghua Yi Xue Za Zhi (Taipei) 64, 259-270.
5. Kruk, P.A., Rampino, N.J. & Bohr, V.A. (1995) DNA damage and repair in telomeres: relation to aging. Proc Natl Acad Sci USA 92, 258-262.
6. Effros, R.B. (2005) Roy Walford and the immunologic theory of aging. Immun Ageing 2, 7.
7. Jeyapalan, J.C. & Sedivy, J.M. (2008) Cellular senescence and organismal aging. Mech Ageing Dev 129, 467-474.
8. Klaunig, J.E. & Kamendulis, L.M. (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44, 239-267.
9. Lubos, E., Handy, D.E. & Loscalzo, J. (2008) Role of oxidative stress and nitric oxide in atherothrombosis. Front Biosci 13, 5323-5344.
10. Roberts, C.K. & Sindhu, K.K. (2009) Oxidative stress and metabolic syndrome. Life Sci 84, 705-712.
11. Dupuis, L. et al. (2004) Mitochondria in amyotrophic lateral sclerosis: a trigger and a target. Neurodegener Dis 1, 245-254.
12. Pratico, D. (2008) Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. Trends Pharmacol Sci 29, 609-615.
13. Cassarino, D.S. & Bennett, J.P., Jr. (1999) An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res Brain Res Rev 29, 1-25.
14. Henchcliffe, C. & Beal, M.F. (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4, 600-609.
15. Emerit, J., Edeas, M. & Bricaire, F. (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58, 39-46.
16. Reeve, A.K., Krishnan, K.J. & Turnbull, D.M. (2008) Age related mitochondrial degenerative disorders in humans. Biotechnol J 3, 750-756.
17. Beal, M.F. (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol 6, 661-666.
18. Rosenberg, R.N. (2002) Mitochondrial therapy for Parkinson disease. Arch Neurol 59, 1523.
19. Block, M.L. (2008) NADPH oxidase as a therapeutic target in Alzheimer's disease. BMC Neurosci 9 Suppl 2, S8.
20. Shults, C.W. et al. (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59, 1541-1550.
21. Zhao, B. (2009) Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease. Neurochem Res 34, 630-638.
22. Dimri, G.P. et al. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92, 9363-9367.
23. Lee, B.Y. (2006) et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5, 187-195.
24. Stockl, P. et al. (2007) Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells. Free Radic Biol Med 43, 947-958.
25. Chen, Q.M., Tu, V.C. & Liu, J. (2000) Measurements of hydrogen peroxide induced premature senescence: senescence-associated beta-galactosidase and DNA synthesis index in human diploid fibroblasts with down-regulated p53 or Rb. Biogerontology 1, 335-339.
26. Lener, T. et al. (2006) Expression profiling of aging in the human skin. Exp Gerontol 41, 387-397.
27. Song, Z., Wang, Y., Xie, L., Zang, X. & Yin, H. (2008) Expression of senescence-related genes in human corneal endothelial cells. Mol Vis 14, 161-170.
28. Welle, S. et al. (2004) Skeletal muscle gene expression profiles in 20-29 year old and 65-71 year old women. Exp Gerontol 39, 369-377.
29. Sherr, C.J. & Roberts, J.M. (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13, 1501-1512.
30. Sharpless, N.E. (2004) Ink4a/Arf links senescence and aging. Exp Gerontol 39, 1751-1759.
31. Famulski, K.S. & Halloran, P.F. (2005) Molecular events in kidney ageing. Curr Opin Nephrol Hypertens 14, 243-248.
32. Carnero, A., Hudson, J.D., Hannon, G.J. & Beach, D.H. (2000) Loss-of-function genetics in mammalian cells: the p53 tumor suppressor model. Nucleic Acids Res 28, 2234-2241.
33. Chainiaux, F., Magalhaes, J.P., Eliaers, F., Remacle, J. & Toussaint, O. (2002) UVB-induced premature senescence of human diploid skin fibroblasts. Int J Biochem Cell Biol 34, 1331-1339.
34. Toussaint, O., Medrano, E.E. & von Zglinicki, T. (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol 35, 927-945.
35. Dumont, P. et al. (2000) Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radic Biol Med 28, 361-373.
36. Chen, Q.M. (2000) Replicative senescence and oxidant-induced premature senescence. Beyond the control of cell cycle checkpoints. Ann NY Acad Sci 908, 111-125.
37. Ben-Porath, I. & Weinberg, R.A. (2005) The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37, 961-976.
38. Liesa, M., Palacin, M. & Zorzano, A. (2009) Mitochondrial dynamics in Mammalian health and disease. Physiol Rev 89, 799-845.
39. Valko, M. et al. (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39, 44-84.
40. Murphy, M.P. (2009) How mitochondria produce reactive oxygen species. Biochem J 417, 1-13.
41. Golden, T.R. & Melov, S. (2001) Mitochondrial DNA mutations, oxidative stress, and aging. Mech Ageing Dev 122, 1577-1589.
42. Kehrer, J.P. (2000) The Haber-Weiss reaction and mechanisms of toxicity. Toxicology 149, 43-50.
43. Squier, T.C. (2001) Oxidative stress and protein aggregation during biological aging. Exp Gerontol 36, 1539-1550.
44. Grivennikova, V.G. & Vinogradov, A.D. (2006) Generation of superoxide by the mitochondrial Complex I. Biochim Biophys Acta 1757, 553-561.
45. Humphries, K.M., Szweda, P.A. & Szweda, L.I. (2006) Aging: a shift from redox regulation to oxidative damage. Free Radic Res 40, 1239-1243.
46. Harman, D. (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11, 298-300.
47. Harman, D. (2009) Origin and evolution of the free radical theory of aging: a brief personal history, 1954-2009. Biogerontology.
48. Yakes, F.M. & Van Houten, B. (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94, 514-519.
49. Stockl, P., Hutter, E., Zwerschke, W. & Jansen-Durr, P. (2006) Sustained inhibition of oxidative phosphorylation impairs cell proliferation and induces premature senescence in human fibroblasts. Exp Gerontol 41, 674-682.
50. Byun, H.O., Kim, H.Y., Lim, J.J., Seo, Y.H. & Yoon, G. (2008) Mitochondrial dysfunction by complex II inhibition delays overall cell cycle progression via reactive oxygen species production. J Cell Biochem 104, 1747-1759.
51. Wei, Y.H., Wu, S.B., Ma, Y.S. & Lee, H.C. (2009) Respiratory Function Decline and DNA Mutation in Mitochondria, Oxidative Stress and Altered Gene Expression during Aging. Chang Gung Med J 32, 113-132.
52. Kwong, L.K. & Sohal, R.S. (2000) Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse. Arch Biochem Biophys 373, 16-22.
53. Shigenaga, M.K., Hagen, T.M. & Ames, B.N. (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91, 10771-10778.
54. Brierley, E.J., Johnson, M.A., James, O.F. & Turnbull, D.M. (1997) Mitochondrial involvement in the ageing process. Facts and controversies. Mol Cell Biochem 174, 325-328.
55. Nair, K.S. (2005) Aging muscle. Am J Clin Nutr 81, 953-963.
56. Boffoli, D. et al. (1994) Decline with age of the respiratory chain activity in human skeletal muscle. Biochim Biophys Acta 1226, 73-82.
57. Conley, K.E., Jubrias, S.A. & Esselman, P.C. (2000) Oxidative capacity and ageing in human muscle. J Physiol 526, 203-210.
58. Yen, T.C., Chen, Y.S., King, K.L., Yeh, S.H. & Wei, Y.H. (1989) Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 165, 944-1003.
59. Boveris, A. & Navarro, A. (2008) Brain mitochondrial dysfunction in aging. IUBMB Life 60, 308-314.
60. Navarro, A. & Boveris, (2008) A. Mitochondrial nitric oxide synthase, mitochondrial brain dysfunction in aging, and mitochondria-targeted antioxidants. Adv Drug Deliv Rev 60, 1534-1544.
61. Wei, Y.H., Lu, C.Y., Lee, H.C., Pang, C.Y. & Ma, Y.S. (1998) Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann NY Acad Sci 854, 155-170.
62. Nagley, P. & Wei, Y.H. (1998) Ageing and mammalian mitochondrial genetics. Trends Genet 14, 513-517.
63. Wei, Y.H. (1992) Mitochondrial DNA alterations as ageing-associated molecular events. Mutat Res 275, 145-155.
64. Pang, C.Y., Lee, H.C., Yang, J.H. & Wei, Y.H. (1994) Human skin mitochondrial DNA deletions associated with light exposure. Arch Biochem Biophys 312, 534-538.
65. Zhang, C., Baumer, A., Maxwell, R.J., Linnane, A.W. & Nagley, P. (1992) Multiple mitochondrial DNA deletions in an elderly human individual. FEBS Lett 297, 34-38.
66. Liu, V.W., Zhang, C. & Nagley, P. (1998) Mutations in mitochondrial DNA accumulate differentially in three different human tissues during ageing. Nucleic Acids Res 26, 1268-1275.
67. Wood, I.S. & Trayhurn, P. (2003) Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 89, 3-9.
68. Brown, G.K. (2000) Glucose transporters: structure, function and consequences of deficiency. J Inherit Metab Dis 23, 237-246.
69. Harris, R.A., Bowker-Kinley, M.M., Huang, B. & Wu, P. (2002) Regulation of the activity of the pyruvate dehydrogenase complex. Adv Enzyme Regul 42, 249-259.
70. Tovar-Mendez, A., Miernyk, J.A. & Randall, D.D. (2003) Regulation of pyruvate dehydrogenase complex activity in plant cells. Eur J Biochem 270, 1043-1049.
71. Klein, D.K. et al. (2007) Lack of AMPKalpha2 enhances pyruvate dehydrogenase activity during exercise. Am J Physiol Endocrinol Metab 293, E1242-1249.
72. Kim, J.W., Tchernyshyov, I., Semenza, G.L. & Dang, C.V. (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3, 177-185.
73. Semenza, G.L., Nejfelt, M.K., Chi, S.M. & Antonarakis, S.E. (1991) Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. Proc Natl Acad Sci USA 88, 5680-5684.
74. Vander Heiden, M.G., Cantley, L.C. & Thompson, C.B. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033.
75. Hsu, P.P. & Sabatini, D.M. (2008) Cancer cell metabolism: Warburg and beyond. Cell 134, 703-707.
76. Robinson, B.H. (2006) Lactic acidemia and mitochondrial disease. Mol Genet Metab 89, 3-13.
77. Ueki, I. et al. (2006) Mitochondrial tRNA gene mutations in patients having mitochondrial disease with lactic acidosis. Mitochondrion 6, 29-36.
78. Finsterer, J. (2007) Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation. Acta Neurol Scand 116, 1-14.
79. Chinnery, P.F., Howell, N., Lightowlers, R.N. & Turnbull, D.M. (1997) Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain 120, 1713-1721.
80. James, A.M., Wei, Y.H., Pang, C.Y. & Murphy, M.P. (1996) Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations. Biochem J 318, 401-407.
81. Zwerschke, W. et al. (2003) Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence. Biochem J 376, 403-411.
82. Prahl, S. et al. (2008) Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care. Biofactors 32, 245-255.
83. Dierick, J.F. et al. (2002) Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence. FEBS Lett 531, 499-504.
84. Ksiazek, K., Breborowicz, A., Jorres, A. & Witowski, J. (2007) Oxidative stress contributes to accelerated development of the senescent phenotype in human peritoneal mesothelial cells exposed to high glucose. Free Radic Biol Med 42, 636-641.
85. Severino, J., Allen, R.G., Balin, S., Balin, A. & Cristofalo, V.J. (2000) Is beta-galactosidase staining a marker of senescence in vitro and in vivo? Exp Cell Res 257, 162-171.
86. Triepels, R.H., Van Den Heuvel, L.P., Trijbels, J.M. & Smeitink, J.A. (2001) Respiratory chain complex I deficiency. Am J Med Genet 106, 37-45.
87. Loeffen, J.L. et al. (2000) Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. Hum Mutat 15, 123-134.
88. Bourgeron, T. et al. (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 11, 144-149.
89. Vanitallie, T.B. (2008) Parkinson disease: primacy of age as a risk factor for mitochondrial dysfunction. Metabolism 57 Suppl 2, S50-55.
90. Orth, M. & Schapira, A.H. (2001) Mitochondria and degenerative disorders. Am J Med Genet 106, 27-36.
91. Herrero, A. & Barja, G. (2000) Localization of the site of oxygen radical generation inside the complex I of heart and nonsynaptic brain mammalian mitochondria. J Bioenerg Biomembr 32, 609-615.
92. Takeshige, K. & Minakami, S. (1979) NADH- and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH-ubiquinone reductase preparation. Biochem J 180, 129-135.
93. Warner, B.B., Stuart, L., Gebb, S. & Wispe, J.R. (1996) Redox regulation of manganese superoxide dismutase. Am J Physiol 271, L150-158.
94. Shin, M.H. et al. (2005) H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo. J Invest Dermatol 125, 221-229.
95. Lu, C.Y., Lee, H.C., Fahn, H.J. & Wei, Y.H. (1999) Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. Mutat Res 423, 11-21.
96. Fulle, S. et al. (2005) Age-dependent imbalance of the antioxidative system in human satellite cells. Exp Gerontol 40, 189-197.
97. Figueiredo, P.A., Powers, S.K., Ferreira, R.M., Appell, H.J. & Duarte, J.A. (2009) Aging impairs skeletal muscle mitochondrial bioenergetic function. J Gerontol A Biol Sci Med Sci 64, 21-33.
98. Judge, S., Jang, Y.M., Smith, A., Hagen, T. & Leeuwenburgh, C. (2005) Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J 19, 419-421.
99. Kondoh, H., Lleonart, M.E., Bernard, D. & Gil, J. (2007) Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization. Histol Histopathol 22, 85-90.
100. Tian, W.N. et al. (1999) Importance of glucose-6-phosphate dehydrogenase activity in cell death. Am J Physiol 276, C1121-1131.
101. Ma, W., Sung, H.J., Park, J.Y., Matoba, S. & Hwang, P.M. (2007) A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr 39, 243-246.
102. Ke, Q. & Costa, M. (2006) Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol 70, 1469-1480.
103. Mansfield, K.D. et al. (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1, 393-399.
104. BelAiba, R.S. et al. (2004) Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells. Biol Chem 385, 249-257.
105. Chandel, N.S. et al. (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95, 11715-11720.
106. Goyal, P. et al. (2004) Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radic Biol Med 36, 1279-1288.
107. Sambandam, N. & Lopaschuk, G.D. (2003) AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. Prog Lipid Res 42, 238-256.
108. Lopaschuk, G.D. (2008) AMP-activated protein kinase control of energy metabolism in the ischemic heart. Int J Obes (Lond) 32 Suppl 4, S29-35.
109. Hardie, D.G. (2004) The AMP-activated protein kinase pathway--new players upstream and downstream. J Cell Sci 117, 5479-5487.
110. Marsin, A.S. et al. (2000) Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol 10, 1247-1255.
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