請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78497完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇慧敏 | zh_TW |
| dc.contributor.advisor | Hui-Min Su | en |
| dc.contributor.author | 林冠甫 | zh_TW |
| dc.contributor.author | Kuan-Fu Lin | en |
| dc.date.accessioned | 2021-07-11T15:00:17Z | - |
| dc.date.available | 2024-10-01 | - |
| dc.date.copyright | 2020-03-13 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Brenna JT, Carlson SE (2014) Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development. J Hum Evol 77:99-106.
Brenna JT, Salem N, Jr., Sinclair AJ, Cunnane SC, International Society for the Study of Fatty A, Lipids I (2009) alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80:85-91. Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D, Kim HY (2009) Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. Journal of neurochemistry 111:510-521. Carnielli VP, Simonato M, Verlato G, Luijendijk I, De Curtis M, Sauer PJ, Cogo PE (2007) Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids. The American journal of clinical nutrition 86:1323-1330. Chung W-L, Chen J-J, Su H-M (2008) Fish oil supplementation of control and (n-3) fatty acid-deficient male rats enhances reference and working memory performance and increases brain regional docosahexaenoic acid levels. The Journal of nutrition 138:1165-1171. Das UN (2006) Essential fatty acids: biochemistry, physiology and pathology. Biotechnology Journal: Healthcare Nutrition Technology 1:420-439. Delarue J, Guriec N (2014) Opportunities to enhance alternative sources of long-chain n-3 fatty acids within the diet. Proc Nutr Soc 73:376-384. Diau G-Y, Hsieh AT, Sarkadi-Nagy EA, Wijendran V, Nathanielsz PW, Brenna JT (2005) The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. BMC medicine 3:11. Gibson RA, Makrides M (1998) The role of long chain polyunsaturated fatty acids (LCPUFA) in neonatal nutrition. Acta Paediatrica 87:1017-1022. Gregory MK, Geier MS, Gibson RA, James MJ (2013) Functional characterization of the chicken fatty acid elongases. J Nutr 143:12-16. Gregory MK, Gibson RA, Cook-Johnson RJ, Cleland LG, James MJ (2011) Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis. PLoS One 6:e29662. Greiner RCS, Winter J, Nathanielsz PW, Brenna JT (1997) Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary α-linolenic and docosahexaenoic acids. Pediatric research 42:826. Guillou H, Zadravec D, Martin PG, Jacobsson A (2010) The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Progress in lipid research 49:186-199. Hamilton JA, Era S, Bhamidipati SP, Reed RG (1991) Locations of the three primary binding sites for long-chain fatty acids on bovine serum albumin. Proceedings of the National Academy of Sciences of the United States of America 88:2051. Hibbeln JR, Salem Jr N (1995) Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. The American journal of clinical nutrition 62:1-9. Horrobin DF (1993) Fatty acid metabolism in health and disease: the role of Δ-6-desaturase. The American journal of clinical nutrition 57:732S-737S. Innis SM (2007) Dietary (n-3) fatty acids and brain development. The Journal of nutrition 137:855-859. James MJ, Ursin VM, Cleland LG (2003) Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n− 3 fatty acids. The American journal of clinical nutrition 77:1140-1145. Kartikasari L, Hughes R, Geier M, Makrides M, Gibson R (2012) Dietary alpha-linolenic acid enhances omega-3 long chain polyunsaturated fatty acid levels in chicken tissues. Prostaglandins, Leukotrienes and Essential Fatty Acids 87:103-109. Kawakita E, Hashimoto M, Shido O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139:991-997. Lauritzen L (2001) The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 40:1-94. Lenihan-Geels G, Bishop K, Ferguson LJN (2013) Alternative sources of omega-3 fats: can we find a sustainable substitute for fish? 5:1301-1315. Majou D (2018) Evolution of the Human Brain: the key roles of DHA (omega-3 fatty acid) and Δ6-desaturase gene. Ocl 25. Martinez M, Ichaso N, Setien F, Durany N, Qiu X, Roesler W (2010) The Delta4-desaturation pathway for DHA biosynthesis is operative in the human species: differences between normal controls and children with the Zellweger syndrome. Lipids Health Dis 9:98. McLennan P, Howe P, Abeywardena M, Muggli R, Raederstorff D, Mano M, Rayner T, Head R (1996) The cardiovascular protective role of docosahexaenoic acid. European journal of pharmacology 300:83-89. Moriguchi T, Greiner RS, Salem Jr N (2000) Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. Journal of neurochemistry 75:2563-2573. Morita M, Imanaka T (2012) Peroxisomal ABC transporters: structure, function and role in disease. Biochim Biophys Acta 1822:1387-1396. Park HG, Park WJ, Kothapalli KS, Brenna JT (2015) The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells. The FASEB Journal 29:3911-3919. Park HG, Engel MG, Vogt-Lowell K, Lawrence P, Kothapalli KS, Brenna JT (2018) The role of fatty acid desaturase (FADS) genes in oleic acid metabolism: FADS1 Δ7 desaturates 11-20: 1 to 7, 11-20: 2. Prostaglandins, Leukotrienes and Essential Fatty Acids 128:21-25. Park WJ, Kothapalli KS, Lawrence P, Tyburczy C, Brenna JT (2009) An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20: 2n-6 and 20: 3n-3. Journal of lipid research 50:1195-1202. Parker G, Gibson NA, Brotchie H, Heruc G, Rees A-M, Hadzi-Pavlovic D (2006) Omega-3 fatty acids and mood disorders. American Journal of Psychiatry 163:969-978. Plourde M, Cunnane SC (2007) Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Applied Physiology, Nutrition, and Metabolism 32:619-634. Pujol A, Ferrer I, Camps C, Metzger E, Hindelang C, Callizot N, Ruiz M, Pampols T, Giros M, Mandel JL (2004) Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy. Hum Mol Genet 13:2997-3006. Rapoport SI, Igarashi M, Gao F (2010) Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis. Prostaglandins Leukot Essent Fatty Acids 82:273-276. Rioux V, Legrand P (2019) Fatty Acid Desaturase 3 (FADS3) Is a Specific∆ 13-Desaturase of Ruminant trans-Vaccenic Acid. Lifestyle Genomics:1-7. Su H-M (2010) Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. The Journal of nutritional biochemistry 21:364-373. Su H-M, Bernardo L, Mirmiran M, Ma XH, Corso TN, Nathanielsz PW, Brenna JT (1999) Bioequivalence of dietary α-linolenic and docosahexaenoic acids as sources of docosahexaenoate accretion in brain and associated organs of neonatal baboons. Pediatric Research 45:87. Tamura K, Makino A, Hullin-Matsuda F, Kobayashi T, Furihata M, Chung S, Ashida S, Miki T, Fujioka T, Shuin T (2009) Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism. Cancer research 69:8133-8140. Tikhonenko M, Lydic TA, Wang Y, Chen W, Opreanu M, Sochacki A, McSorley KM, Renis RL, Kern T, Jump DB (2010) Remodeling of retinal fatty acids in an animal model of diabetes: a decrease in long-chain polyunsaturated fatty acids is associated with a decrease in fatty acid elongases Elovl2 and Elovl4. Diabetes 59:219-227. van Roermund CW, Visser WF, Ijlst L, Waterham HR, Wanders RJ (2011) Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid beta-oxidation. Biochim Biophys Acta 1811:148-152. Walker CG, Jebb SA, Calder PC (2013) Stearidonic acid as a supplemental source of omega-3 polyunsaturated fatty acids to enhance status for improved human health. Nutrition 29:363-369. Waterham HR, Ferdinandusse S, Wanders RJ (2016) Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta 1863:922-933. Zhang JY, Kothapalli KS, Brenna JT (2016) Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis. Curr Opin Clin Nutr Metab Care 19:103-110. Zhang JY, Qin X, Liang A, Kim E, Lawrence P, Park WJ, Kothapalli KS, Brenna JT (2017) Fads3 modulates docosahexaenoic acid in liver and brain. Prostaglandins, Leukotrienes and Essential Fatty Acids 123:25-32. Zhao H, Matsuzaka T, Nakano Y, Motomura K, Tang N, Yokoo T, Okajima Y, Han S-i, Takeuchi Y, Aita Y (2017) Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes 66:1833-1846. Zouboulis C, Jourdan E, Picardo M (2014) Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. Journal of the European Academy of Dermatology and Venereology 28:527-532. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78497 | - |
| dc.description.abstract | 二十二碳六烯酸 (docosahexaenoic acid, DHA, 22:6n-3) 為n-3多元不飽和脂肪酸，主要富含在腦部神經細胞膜中，對維持神經細胞正常結構及功能十分重要。DHA可以經由前驅物α-次亞麻油酸 （α-linolenic acid, ALA, 18:3n-3），透過去飽和酶 (fatty acid desaturase, FADS)及延長酶 (elongase of very long chain fatty acid, ELOVL)經由一系列去飽和及加長碳鏈後生成。在大腦發育時期，嬰兒有能力自行合成DHA，但成年之後DHA在人體中的合成效率卻很低，因此本論文研究是否因人類細胞中缺乏特定的酵素而導致無法有效合成DHA，又能否透過強迫表現該酵素來克服。
本論文選用了MCF-7、SH-SY5Y及HEK293T三種人類細胞株，加入不同的DHA前驅物ALA、EPA (20:5n-3)、DPA (22:5n-3)、24:5n-3或24:6n-3培養後，以氣相層析儀分析其脂肪酸組成，並對照參與DHA合成相關酵素FADS2、FADS1、ELOVL5及ELOVL2之即時聚合酶鏈鎖反應結果，找出各細胞中限制DHA合成之酵素。 本論文發現MCF-7主要缺乏FADS2；SH-SY5Y主要缺乏ELOVL2；HEK293T則是FADS2及ELOVL2兩種都缺乏，導致無法合成DHA。而當MCF-7強迫表現FADS2、SH-SY5Y強迫表現ELOVL2或HEK293T同時強迫表現FADS2及ELOVL2可以使該細胞株DHA合成效率顯著增加。 故本論文推論：在參與DHA合成的一系列酵素中，FADS2或ELOVL2缺乏是成人無法有效率合成DHA的主要原因。 | zh_TW |
| dc.description.abstract | Docosahexaenoic acid (DHA, 22:6n-3) is mainly enriched in the brain and is essential for normal neurological function. DHA is converted from its precursor α-linolenic acid (ALA, 18:3n-3) by a series of long chain fatty acid desaturases (FADS2 and FADS1) and elongases (ELOVL2 and ELOVL5). During brain development, infant has the ability to synthesize DHA, while in adult, DHA biosynthesis is low. We then studied whether some specific enzymes involved the DHA biosynthesis may be defected, and this defection can be overcome by its overexpression. The human cell lines, SH-SY5Y, MCF-7 and HEK 293T were incubated with DHA precursors, ALA, EPA (20:5n-3), DPA (22:5n-3), 24:5n-3 or 24:6n-3 to examine the potential defected enzymes to block DHA biosynthesis. The fatty acid composition was analyzed by gas chromatography with flame ionization dectector. The enzymes involved in DHA biosynthesis, FADS2, FADS1, ELOVL5 and ELOVL2 mRNA expression were analyzed by RT-qPCR. We found the mainly defected enzymes involved DHA biosynthesis was ELOVL2 in SH-SY5Y, FADS2 in MCF-7 or both FADS2 and ELOVL2 in HEK 293T. The DHA biosynthesis from its precursors were recovered by the overexpressed FADS2 or ELOVL2, or FADS2 plus ELOVL2 in MCF-7, SH-SY5Y or HEK 293T, respectively. It is suggested that FADS2 or/and ELOVL2 may be defected for the DHA biosynthesis in adults. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:00:17Z (GMT). No. of bitstreams: 1 ntu-108-R05441015-1.pdf: 3362842 bytes, checksum: f78a79d1145306f2a46fea37399c8184 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 目錄 III 圖目錄 V 表目錄 VI 第一章、文獻回顧 1 一、 二十二碳六烯酸簡介 1 二、 DHA合成路徑 2 三、 參與多元不飽和脂肪酸合成的相關酵素 3 四、 DHA的合成效率 5 第二章、研究目的與實驗設計 7 一、 研究目的 7 二、 實驗設計 7 第三章、材料與方法 8 一、 細胞培養 8 二、 細胞解凍 9 三、 細胞繼代 10 四、 細胞存活率測試 10 五、 質體建構 11 六、 細胞轉染 12 七、 以流式細胞術測量細胞轉染效率 13 八、 以即時聚合酶連鎖反應分析基因表現量 14 九、 以氣相層析分析脂肪酸組成 16 十、 以西方墨點法分析蛋白質表現量 18 十一、 白蛋白鍵結之不飽和脂肪酸配置 23 第四章、實驗結果 25 一、 比較SH-SY5Y, MCF-7及HEK293T細胞株中，參與DHA合成相關 酵素之基因表現.………………………………………………………25 二、 探討SH-SY5Y, MCF-7及HEK293T細胞株對DHA的吸收及合成能 力…….…………………………………………………………………26 三、 合成DHA可能瓶頸 27 四、 在SH-SY5Y, MCF-7及HEK293T中強迫表現FADS2或ELOVL2以 及同時強迫表現FADS2及ELOVL2對合成DHA的影響………....30 第五章、討論 35 一、 Tracer-study實驗設計 35 二、 探討人類細胞株為何無法有效合成DHA 35 三、 FADS2及ELOVL2在細胞株合成DHA的重要性 36 四、 FADS2基因的Δ4 desaturase活性 37 五、 C3A/HepG2及MDA-MB231轉染FADS2+ELOVL2不影響DHA 合成效率........………………………………………………………….38 六、 細胞株轉染FADS2促進16:0合成16:1 40 七、 ABC transporter D2 (ABCD2) 缺乏不影響DHA合成 40 第六章、結論 41 圖 (Figure) 42 表 (Table) 56 附錄 (Appendix) 65 參考文獻 (Reference) 73 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 探討長鏈脂肪酸去飽和酶及延長酶強迫表現對三種人類細胞株合成二十二碳六烯酸之影響 | zh_TW |
| dc.title | Effect of long chain fatty acid desaturase and elongase overexpression on docosahexaenoic acid biosynthesis in three human cell lines | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 108-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃青真;張美鈴;呂紹俊 | zh_TW |
| dc.contributor.oralexamcommittee | Ching-jang Huang;Mei-Ling Chang;Shao-Chun Lu | en |
| dc.subject.keyword | 二十二碳六烯酸,n-3多元不飽和脂肪酸,脂肪酸去飽和?,脂肪酸延長?, | zh_TW |
| dc.subject.keyword | DHA,n-3PUFA,FADS,ELOVL, | en |
| dc.relation.page | 76 | - |
| dc.identifier.doi | 10.6342/NTU201904167 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-10-01 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 生理學研究所 | - |
| dc.date.embargo-lift | 2029-09-27 | - |
| 顯示於系所單位： | 生理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-1.pdf 目前未授權公開取用 | 3.28 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。