請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77227完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張明富(Ming-Fu Chang) | |
| dc.contributor.author | Lok-Si Kong | en |
| dc.contributor.author | 江樂施 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:51:47Z | - |
| dc.date.available | 2021-07-10T21:51:47Z | - |
| dc.date.copyright | 2019-08-29 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-15 | |
| dc.identifier.citation | 1. Aggleton JP, Vann SD, Denby C, Dix S, Mayes AR, Roberts N, Yonelinas AP. (2005). Sparing of the familiarity component of recognition memory in a patient with hippocampal pathology. Neuropsychologia. 43, 1810-1823.
2. Belfiore A1, Frasca F, Pandini G, Sciacca L, Vigneri R. (2009). Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev. 30, 586-623. 3. Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD. (1991). ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 65, 663-675. 4. Buers I, Pennekamp P, Nitschke Y, Lowe C, Skryabin BV, Rutsch F. (2016). Lmbrd1 expression is essential for the initiation of gastrulation. J Cell Mol Med. 20, 1523-1533. 5. Chiu YL. (2007). Functional analysis of the putative actin-biding domain of NESI protein. NTU. 6. Chang YT. (2017). LMBD1 protein regulates dopamine uptake through interacting with dopamine transporter and autoreceptor D2. NTU. 7. Chen XY, Cai HZ, Wang XY, Chen QY, Yang H2 Chen YJ, Tang YP. (2015). Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments. Genet Mol Res. 28, 18325-18333. 8. Chong WP, Sim LC, Wong KT, Yap MG. (2009). Enhanced IFNgamma production in adenosine-treated CHO cells: a mechanistic study. Biotechnol Prog. 25, 86673. 9. Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I, Suormala T, Burda P, Frapolli M, Stucki M, Nürnberg P, Thiele H, Robenek H, Höhne W, Longo N, Pasquali M, Mengel E, Watkins D, Shoubridge EA, Majewski J, Rosenblatt DS, Fowler B, Rutsch F, Baumgartner MR. (2012). Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet. 44, 1152-1155. 10. Eguchi S, Iwasaki H, Ueno H, Frank GD, Motley ED, Eguchi K, Marumo F, Hirata Y, Inagami T. (1999). Intracellular signaling of angiotensin II induced p70S6 kinase phosphorylation at Ser 411 in vascular smooth muscle cells. J Biol Chem. 274, 36843-36851. 11. Frangioni JV, Beahm PH, Shifrin V, Jost CA, Neel BG. (1992). The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell. 68, 545-560. 12. Hamm RJ, Pike BR, O'Dell DM, Lyeth BG, Jenkins LW. (1994). The rotarod test: an evaluation of its effectiveness in assessing motor deficits. J Neurotrauma. 11, 187-196. 13. Hepler DJ, Wenk GL, Cribbs BL, Olton DS, Coyle JT. (1985).Memory impairments following basal forebrain lesions. Brain Res. 346, 8-14. 14. Hsu WT. (2010). Functional analysis of LMBRD1 in neuronal differentiation. NTU. 15. Hsu KH. (2018). The transcriptional regulation of LMBRD1 gene in neuron cell differention. NTU. 16. Huang C, Jiang JY, Chang SC, Tsay YG, Chen MR, Chang MF. (2013). Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen. J Virol. 87, 1596-5604. 17. Jackson LP, Kelly BT, McCoy AJ, Gaffry T, James LC, Collins BM, Höning S, Evans PR, Owen DJ. (2010). A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex. Cell. 141, 1220–1229. 18. Jefferies HB, Fumagalli S, Dennis PB, Reinhard C, Pearson RB, Thomas G. (1997). Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k. EMBO J. 16, 3693-704. 19. Jessica S. Kelsey, Nathan M. Fastman, and Daphne D. Blumberg. (2012). Evidence of an Evolutionarily Conserved LMBR1 Domain-Containing Protein That Associates with Endocytic Cups and Plays a Role in Cell Migration in Dictyostelium discoideum. Eukaryot Cell. 11, 401-416. 20. Park JH, Ku HJ, Kim JK, Park JW and Lee JH. (2018). Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin. Scientific Reports, 8:9464. 21. Porta C, Paglino C, Mosca A. (2014). Targeting PI3K/Akt/mTOR Signaling in Cancer. Front Oncol. 4, 64. 22. Karen M. Rodrigue, Naftali Raz. (2004). Shrinkage of the Entorhinal Cortex over Five Years Predicts Memory Performance in Healthy Adults. J. Neurosci. 24, 956-963. 23. Kadlecova Z, Spielman SJ, Loerke D, Mohanakrishnan A, Reed DK, Schmid SL. (2017). Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2. J Cell Biol. 1, 167-179. 24. Kelsey JS, Fastman NM, and Blumberg DD. (2012). “Evidence of an evolutionarily conserved LMBR1 domain-containing protein that associates with endocytic cups and plays a role in cell migration in dictyostelium discoideum.,” Eukaryot. Cell. 11, 401–416. 25. Kirchhausen T, Owen D, Harrison SC. (2014). Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb Perspect Biol. 6, a016725. 26. Kosaka T, Ikeda K. (1983). Possible temperature-dependent blockage of synaptic vesicle recycling induced by a single gene mutation in Drosophila. J Neurobiol. 3, 207-225. 27. Kyriakis JM, Avruch J. (2001). Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2, 807-869. 28. Lee YJ. (2018). Roles of LMBD1 protein in cell migration of mouse embryonic fibroblasts. NTU. 29. Lemmon MA, Schlessinger J. (2010). Cell signaling by receptor tyrosine kinases. Cell. 25, 1117-1134. 30. Lettice LA, Horikoshi T, Heaney SJ, van Baren MJ, van der Linde HC, Breedveld GJ, Joosse M, Akarsu N, Oostra BA, Endo N, Shibata M, Suzuki M, Takahashi E, Shinka T, Nakahori Y, Ayusawa D, Nakabayashi K, Scherer SW, Heutink P, Hill RE, Noji S. (2002). Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natl Acad Sci U S A. 99, 7548-7553. 31. Li Z, Song Y, Liu L, Hou N, An X, Zhan D, Li Y, Zhou L, Li P, Yu L, Xia J, Zhang Y, Wang J, Yang X. (2017). miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation. Cell Death Differ. 7, 1205-1213. 32. Lin JW, Ju W, Foster K, Lee SH, Ahmadian G, Wyszynski M, Wang YT, Sheng M. (2000). Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization. Nat. Neurosci. 3, 1282–1290. 33. Li YP. (2005). Biochemical characterization of NESI protein involved in the nuclear export pathway. NTU. 34. Lin CY. (2014). Roles of LMBD1 protein in retinoic acid- induced dendritic spine formation. NTU. 35. Lin YH. (2016). The mechanism of LMBD1 protein involved in neuronal spine formation. NTU. 36. Lips DJ, deWindt LJ, van Kraaij DJ, Doevendans PA. (2003). Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy. Eur Heart J. 10, 883-96. 37. Lips DJ, Bueno OF, Wilkins BJ, Purcell NH, Kaiser RA, Lorenz JN, Voisin L, Saba-El-Leil MK, Meloche S, Pouysségur J, Pagès G, De Windt LJ, Doevendans PA, Molkentin JD. (2004). MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo. Circulation. 109, 1938–1941. 38. Lu CY. (2012). LMBRD1 regulates the subcellular localizations of nucleocytoplasmic transport proteins CAS and importin a. NTU. 39. Liu PF. (2016). The role of LMBRD1 gene involved in myogensis. NTU. 40. Ma L, Chen Z., Erdjument-Bromage H., Tempst P. Pandolfi PP. (2005). Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell. 121, 179–193. 41. Marandi S1, De Keyser N, Stilmant C, Saliez A, Sokal EM, Guiot Y, Buts JP. (2002). Ontogeny of MAP kinases in rat small intestine: premature stimulation by insulin of BBM hydrolases is regulated by ERKs but not by p-38 MAP kinase. Pediatr Res. 52, 180-188. 42. McKinsey TA, Olson EN. (2005). Toward transcriptional therapies for the failing heart: chemical screens to modulate genes. J Clin Invest. 3, 538-46. 43. Meier R, Alessi DR, Cron P, Andjelković M and Hemmings BA. (1997). Mitogenic activation phosphorylation, and nuclear translocation of protein kinase B. J Biol Chem. 272, 30491-30497. 44. Pan KH. (2017). The C-terminal domain of LMBD1 protein is critical for the insulin receptor signaling. NTU. 45. Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G. (2000) Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. 6815, 994-997. 46. Rodrigue KM, Raz N. (2004). Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults. J Neurosci. 4, 956-963. 47. Rose N, Myerson J, Roediger HL, Hale S. (2010). Similarities and differences between working memory and long-term memory: Evidence from the levels-of-processing span task. Journal of Experimental Psychology: Learning, Memory, and Cognition, 36, 471–483. 48. Rutsch F, Gailus S, Miousse IR, Suormala T, Sagné C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Höhne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P. (2009). Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nat Genet. 41, 234-239. 49. Nobata S, Ventura A, Kaiya H, and Takei Y. (2010). Diversified cardiovascular actions of six homologous natriuretic peptides (ANP, BNP, VNP, CNP1, CNP3, and CNP4) in conscious eels. Am J Physiol Regul Integr Comp Physiol. 298, 1549–1559. 50. Saltiel AR, Kahn CR. (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414, 799-806. 51. Schwenk F1, Baron U, Rajewsky K. (1995). A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res. 23, 5080-5081. 52. Sciarretta S, Forte M, Frati G, Sadoshima J. (2018). New insights into the role of mTOR signaling in the cardiovascular system. Circ. Res. 122, 489–505. 53. Manivasagam S, Subramanian V, Tumala A and Vellaichamy E. (2016). Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats. Mol. Cell Endocrinol. 433, 117-129. 54. Manivasagam S, Subramanian V, Tumala A and Vellaichamy E. (2017). Valporic acid enhances the Atrial Natriuretic Peptide (ANP) mediated anti-hypertrophic activity by modulating the Npr1 gene transcription in H9c2 cells in vitro. Mol. Cell Endocrinol. 813, 94-104. 55. Ta YC. (2013).Mechanisms of LMBD1 and its associatedprotein involved in the vitamin B12 transport. NTU. 56. Tosoni D, Puri C, Confalonieri S, Salcini AE, De Camilli P, Tacchetti C, Di Fiore PP. (2005). TTP specifically regulates the internalization of the transferrin receptor. Cell. 5, 875-888. 57. Traub LM. (2009) Tickets to ride: selecting cargo for clathrin-regulated internalization. Nat. Rev. Mol. Cell Biol. 10, 583–596 58. Tseng LT, Lin CL, Tzen, KY., Chang, SC. and Chang, MF. (2013).LMBD1 protein serves as a specific adaptor for insulin receptor internalization. J. Biol. Chem. 288, 32424-32432. 59. Tseng LT, Lin CL, Pan KH, Tzen KY, Su MJ, Tsai CT, Li YH, Li PC, Chiang FT, Chang SC, Chang MF. (2018). Single allele Lmbrd1 knockout results in cardiac hypertrophy. J Formos Med Assoc. 117, 471-479. 60. Wang J, Xu N, Feng X, Hou N, Zhang J, Cheng X, Chen Y, Zhang Y, Yang X. (2005). Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure. Circ Res. 97, 821-828. 61. Wang YH, Chang SC, Huang C, Li YP, Lee CH, Chang MF. (2005) Novel nuclear export signal-interacting protein, NESI, critical for the assembly of hepatitis δ virus. J. Virol. 79, 8113–8120. 62. Warren RA, Green FA, Enns CA. (1997) Saturation of the endocytic pathway for the transferrin receptor does not affect the endocytosis of the epidermal growth factor receptor. J. Biol. Chem. 272, 2116–2121. Weng QP, Kozlowski M, Belham C, Zhang A, Comb MJ, Avruch J. (1998). Regulation of the p70S6 kinase by phosphorylation in vivo. J Biol Chem. 273, 16621- 16629. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77227 | - |
| dc.description.abstract | LMBD1為Limb region 1 domain containing 1 gene (LMBRD1) 所轉譯的蛋白質，含有540個胺基酸的膜蛋白且具有九個穿膜區域 (transmembrane domain)，主要分佈於細胞膜、溶酶體膜及內質網上。先前LMBD1已被報導參與在維生素B12從溶酶體釋出至細胞質，本實驗室研究亦指出LMBD1蛋白質在胰島素受體 (insulin receptor; IR) 的內吞作用中扮演作為轉接器 (adaptor) 的角色，但不參與轉鐵蛋白質受體 (transferrin receptor; TrfR) 之內吞作用。另外，配合18F-FDG靜脈注射，在正子發射斷層掃描 (PET) 發現在Lmbrd1+/-小鼠心臟葡萄糖有高於wild type的現象。同時也觀察到Lmbrd1+/-小鼠其心臟有左心室肥大 (cardiac hypertrophy) 的症狀出現，並且在年齡較大時發生心臟收縮性功能障礙，顯示LMBD1蛋白質可能在心臟發育上扮演一個重要的角色。本研究主要探討在Lmbrd1+/-小鼠模式造成心室肥大的過程中，Lmbrd1基因是否透過參與胰島素受體訊息傳遞路徑調控心肌細胞的肥大。結果顯示，在Lmbrd1+/-基因剔除小鼠模式中觀察到其心臟組織IR、Akt及mTOR的磷酸化相較於wild type有上升的現象，並且心臟重量與脛骨長度比值也高於wild type，以rapamycin抑制mTOR的活化後Lmbrd1+/-小鼠的心臟大小恢復正常，心臟重量與脛骨長度比值也下降。同時，在大鼠的心肌母細胞H9C2中Lmbrd1基因表現下降時也觀察到IR及mTOR的磷酸化上升。在GST-pull down assay證實LMBD1會透過其羧基端 (胺基酸433-493) 與胰島素受體結合。利用dithiothreitol 和 2-mercaptoethanol破壞胰島素受體與β subunit間的雙硫鍵結，結果發現LMBD1會透過其羧基端與胰島素受體之β subunit作結合，但與 subunit 並沒有直接交互作用。GST-LMBD1 (胺基酸433-493) 競爭內生性之LMBD1蛋白質與胰島素受體結合，會使胰島素受體下游訊息傳遞路徑Akt磷酸化上升。綜合實驗結果可以推測Lmbrd1基因透過活化IR/Akt/mTOR的訊息傳遞路徑，導致Lmbrd1+/-小鼠出現心肌肥大症狀，而LMBD1羧基端可能在IR之內吞作用中扮演選擇性的角色。 | zh_TW |
| dc.description.abstract | LMBD1 protein is encoded by the limb region 1 domain containing 1 gene (LMBRD1) and consists of 540 amino acids residues with nine putative transmembrane domains. LMBD1 distributes over plasma membrane, ndoplasmic reticulum and lysosome. Previous study has shown that LMBD1 is involved in aiding the export of cobalamin from lysosome to the cytosol. In addition, our previous study demonstrated that LMBD1 is a specific adaptor for the insulin receptor (IR) endocytosis. The relactive 18F-FDG uptake in Lmbrd1+/- mouse herats was higher than that of the wildtype littermates. Lmbrd1 ubiquitous heterozygous knockout (Lmbrd1+/-) mice displayed cardiac hypertrophy and developed systolic cardiac dysfunction at an older age. These data suggest that LMBD1 is a critical component in the development of heart. This study aims to examine whether Lmbrd1 gene regulates cardiomyocyte hypertrophy through the insulin receptor signaling pathway and exhibits ventricular hypertrophy in Lmbrd1+/- mouse model. Results showed that IR kinase, along with its downstream signaling protein kinase Akt and mTOR, was hyperphosphorylated in Lmbrd1+/- mouse hearts. In addation, the ratio of heart weight to tibia length was increased in Lmbrd1+/- mice. When Lmbrd1+/- mice were treated with mTOR inhibitor rapamycin, the ratio of heart weight to tibia length decreased and heart size became normal. Furthrtmore, the phosophorylation of IR and mTOR were increasd in Lmbrd1 gene knocked down H9C2 cells. Moreover, the GST-pull down demonstrated an interacton of C-terminal domain of LMBD1 with the IR. Further studing using dithiothreitol and 2-mercaptoethanol to reduce disulfide bonds betweenIR subunits, results showed that GST-LMBD1(433-493) interacted with the subunit of IR. No direct interaction between LMBD1 and the subunit of IR was observed. In addition, GST-LMBD1(433-493) competed with endogenous LMBD1 for interacting with IR and increased Akt phosphorylation, a downstream of IR signaling pathway. These data suggest that Lmbrd1+/- mice exhibit mTOR activation through IR-Akt axis, resulting in the progression of ventricular hypertrophy. In addation, LMBD1 interacts with IR through its subdomain from amino acid residues 433 to 493, with cargo selectivity in the IR endocytosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:51:47Z (GMT). No. of bitstreams: 1 ntu-108-R06442032-1.pdf: 2606533 bytes, checksum: 55905d5ab8f7648ec578741c1c46a750 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 目次……………………………………………………………………………………I
中文摘要………………………………………………………………………………IV 英文摘要………………………………………………………………………………V 縮寫表…………………………………………………………………………………VII 緒論………………………………………………………………………………….…1 一、 LMBRD1基因相關研究……………………………………………………1 1.LMBRD1基因剔除小鼠之表現……………………………………….……1 2.LMBD1………………………………………………………………………2 3.NESI…………………………………………………………………………………6 二、胰島素受體在心臟葡萄糖吸收所扮演的角色…………………………..…7 三、依賴網格蛋白的胞吞作用 (clathrin-mediated endocytosis) …………………8 1.胞吞作用………………………………………………………………….…8 2.Clathrin coated pits (CCP)的形成………………………………………...…8 3.Adaptor protein-2 (AP-2) …………………………………………………....9 四、 心臟肥厚的機制……………………………………………………………...9 1.心臟肥厚的概論………………………………………………………………9 2.心臟肥厚之訊息傳遞路徑…………………………………………………………10 材料來源……………………………………………………………………………….12 一、藥品……………………………………………………………………….…12 二、酵素……………………………………………………………………….…15 三、抗體……………………………………………………………………….…15 1.初級抗體 (primary antibody) …………………………………………….….15 2.次級抗體 (secondary antibody) …………………………………………..…16 四、細胞培養液及試劑…………………………………………………………16 五、細胞株………………………………………………………………………17 六、套組試劑……………………………………………………………………17 七、質體…………………………………………………………………………18 八、引子…………………………………………………………………………19 研究主題………………………………………………………………………………20 實驗方法………………………………………………………………………………21 一、小鼠基因型鑑定分析………………………………………………………21 1.小鼠基因體DNA (genomic DNA)之製備…………………………….……21 2.聚合酶鏈鎖反應 (polymerase chain reaction, PCR) ………………21 3.DNA瓊脂膠電泳…………………………………………………………22 二、勝任細胞 (competent cells)的製備……………………………………23 三、細菌轉型 (Transformation)…………………………………………23 四、質體的小量質備 (Mini preparation of plasmid DNA)……24 五、質體的中量質備 (Midi preparation of plasmid DNA)……25 六、細胞株繼代培養………………………………………………………25 七、細胞內RNA之收集…………………………………………………26 八、反轉錄聚合酶反應 (Reverse transcription-PCR) …………………27 九、即時聚合酶連鎖反應 (real-time PCR) ……………………………27 十、DNA轉染 (DNA transfection) ……………………………………….27 1.HEK293T DNA transfection…………………………………………………27 2.H9C2 DNA transfection…………………………………………………28 十一、細胞內蛋白質之收集………………………………………………28 十二、組織內蛋白質之收集………………………………………………29 十三、蛋白質定量……………………………………………………………29 十四、正十二烷硫酸鈉—聚丙烯醯胺膠體電泳(SDS-PAGE) ………………29 十五、Coomassie brilliant blue (CBR) 染色法………………………30 十六、西方墨點法 (Western blot analysis) …………………………31 1.蛋白質轉漬 (protein transfer) ………………………………………………31 2.抗體與membrane 進行反應……………………………………………31 3.偵測蛋白質…………………………………………………………………31 4.脫去反應……………………………………………………………………32 十七、免疫沉澱 (Immunoprecipitation) ………………………………………32 十八、GST融合蛋白質之表現與純化……………………………………………33 1.小量誘導檢測融合蛋白質表現…………………………………………33 2.大量誘導檢測融合蛋白質表現…………………………………………..…33 十九、GST-pull down assay………………………………………………………..34 二十、帶有shRNA之VSV-G pseudotyped lentivirus 感染……………34 二十一、小鼠心臟灌流…………………………………………………………35 二十二、統計分析……………………………………………………………….…35 實驗結果………………………………………………………………………….36 一、探討Lmbrd1+/-基因剔除小鼠心臟組織中Insulin receptor、Akt和mTOR磷酸化程度……………………………………………………36 二、mTOR的磷酸化對心肌肥厚的影響……………………………...…37 三、利用shRNA knockdown H9C2細胞株中LMBD1之表現量以探討對mTOR和Akt磷酸化之影響……………………………………...….37 四、LMBD1之胺基酸433-493片段可與IR之 β subunit結合……….38. 五、探討LMBD1與內生性IR之 subunit之交互作用……………39 六、GST-LMBD1(433-493)蛋白質干擾內生性LMBD1蛋白質與 IR之結合使H9C2細胞株之Akt磷酸化增加……………………………….39 討論……………………………………………………………………………40 一、LMBD1蛋白質與IR/Akt/mTOR 訊息傳遞路徑之關鏈性…………41 二、LMBD1蛋白質與IR之交互作用關係………………………………42 三、LMBD1調控心肌細胞的肥大是否獨立依賴IR/Akt/mTOR訊息傳遞路徑……………………………………………………………………43 四、結語……………………………………………………………………44 圖表…………………………………………………………………………….….….45 參考文獻………….……………………………………………………………….….61 | |
| dc.language.iso | zh-TW | |
| dc.subject | LMBD1蛋白質 | zh_TW |
| dc.subject | 心室肥大 | zh_TW |
| dc.subject | 胰島素受體的訊息傳遞 | zh_TW |
| dc.subject | insulin receptor signaling | en |
| dc.subject | cardiac hypertrophy | en |
| dc.subject | LMBD1 protein | en |
| dc.title | LMBD1蛋白質參與胰島素受體的訊息傳遞及心室肥大之機制 | zh_TW |
| dc.title | The mechanism of LMBD1 protein involved in the regulation of insulin receptor signaling and cardiac hypertrophy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 詹迺立(Nei-Li Chan),曾秀如(Shiou-Ru Tzeng),劉旻禕(Helene Minyi Liu) | |
| dc.subject.keyword | LMBD1蛋白質,胰島素受體的訊息傳遞,心室肥大, | zh_TW |
| dc.subject.keyword | LMBD1 protein,insulin receptor signaling,cardiac hypertrophy, | en |
| dc.relation.page | 66 | |
| dc.identifier.doi | 10.6342/NTU201903135 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2019-08-15 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-R06442032-1.pdf 未授權公開取用 | 2.55 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。