簡易檢索 / 詳目顯示

研究生: 邱芷葳
Chiu, Chih-Wei
論文名稱: 同位素化學標記法搭配質譜技術進行發炎反應動物模式之差異蛋白質體學研究
Differential Proteomics of Monosodium Urate Crystals-Induced Responses in Dissected Murine Air Pouch Membranes by iTRAQ Technology
指導教授: 陳頌方
Chen, Sung-Fang
學位類別: 博士
Doctor
系所名稱: 化學系
Department of Chemistry
論文出版年: 2015
畢業學年度: 103
語文別: 英文
論文頁數: 124
中文關鍵詞: 二維分離液相層析質譜差異蛋白質體學痛風
英文關鍵詞: Two-dimensional separation, Pulsed-Q dissociation, Monosodium urate crystal
論文種類: 學術論文
相關次數: 點閱:121下載:18
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 無中文摘要

    Proteomics is a large-scale comprehensive study of a specific proteome, including information on the levels of different types of proteins, their modifications and variations, as well as their interactions and networks, in order to understand biological processes. Recent successes clearly show that mass spectrometry-based proteomics as an essential tool for molecular and cellular biology and for the rising field of systems biology. Two-dimensional fractionation is a useful tool to increase proteome coverage and the dynamic range than single-dimensional LC. In part I of this dissertation, various peptide fractionation strategies that are used for 2D (two-dimensional) separations were evaluated. The use of SCX x RPLC for desalted samples provided superior results in protein identification. These approaches are complementary and allowed 43% more peptides to be identified, when compared with a single fractionation strategy. In part II, LTQ-PQD parameters were optimized in order to used isobaric tags technology for quantitative proteomics. The number of microscans and the target value are the most critical factors in producing intense reporter ions for quantitation. The appropriate normalized collisional energy range for PQD could be very narrow and must be carefully determined. The optimized LTQ-PQD parameters were introduced to a murine air pouch membrane in part III. iTRAQ-based approach coupled with offline 2D LC-MS/MS proteomics technology was applied to analyze the protein expression profile using an inflamed murine air pouch membrane as a model. Statistical analyses revealed that 317 proteins are differentially expressed, at least at one time point, after the MSU treatment, that they are mainly involved in the complement system and activation of NALP3 inflammasome. Moreover, the TCA cycle was found to be down-regulated at both the translational and transcriptional levels. Lastly, pyruvate carboxylation was found to be a potential target for an anti-gout treatment. These results provide novel insights into the nature of gouty inflammation.

    Table of Content i List of Tables iv List of Figures v ABBREVIATIONS vii ABSTRACT x INTRODUCTION 1 Peptide Fractionation 1 Differential Proteomics 5 Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) 6 Pulsed-Q Dissociation (PQD) 6 Monosodium Urate Crystals-Induced Responses in Dissected Murine Air Pouch Membranes 7 EXPERIMENTAL SECTION 11 Chemicals 11 Sample Preparation and Digestion of PLC/PRF/5 lysate 11 Protein Standard Mixture Preparation and iTRAQ Reagent Labeling for LTQ-PQD optimization 12 Murine Air Pouches 13 Dissection of the Air Pouch Membrane 14 Air Pouch Membrane Protein Extraction 14 Murine Air Pouch Sample Pretreatment Preparation and iTRAQ Reagent Labeling 15 Analytical Setups for Peptide from the PLC/PRF/5 Lysate Pretreatment 16 Analytical Setups for First-Dimension Separation for the PLC/PRF/5 Lysate Sample 16 SCX Chromatography 17 HILIC Chromatography 18 Reverse Phase Chromatography at Low pH 18 Reverse Phase Chromatography at High pH 19 Solution-IEF Separation 20 LC-MS/MS Analysis 21 LC-MS/MS Analysis by LTQ-PQD 22 Peptide and Protein Identification and Quantitation 23 Western Blotting 25 Treatment of THP-1 Cells with a Suspension of MSU Crystals 25 Total RNA Isolation, Reverse Transcription, Real Time PCR Quantification of Genes 26 RESULTS AND DISCUSSION 27 Part I - Evaluation of Peptide Fractionation Strategies used in Proteome Analysis. 27 The Influence of Salt on Separation Efficiency 28 Orthogonality of Two-Dimensional Separations 29 Charge, GRAVY and pI Value Distribution of Peptides 31 Complementarity of SCX x RPLC, HILIC x RPLC, Alkaline-RP x RPLC and sIEF x RPLC Methods 33 Summary 36 PART II - Optimization of Pulsed-Q Dissociation Parameters in Linear Ion Trap Mass Spectrometer for iTRAQ Quantitation 37 Effects of Microscan and Target Value 37 Effects of Normalized Collisional Energy 38 Effects of Activation Q and Delay Time 39 Summary 41 PART III - Differential Proteomics of Monosodium Urate Crystals-Induced Responses in Dissected Murine Air Pouch Membranes by iTRAQ Technology 42 iTRAQ Proteomics Profiling of MSU Crystals in the Air Pouch Membrane by 2D LC-MS/MS Analysis 43 MSU Crystals Stimulated the Alternative Pathway of the Complement System 45 Up-Regulated Proteins Related to NALP3 Inflammasome 47 The TCA Cycle Is Down-Regulated at Transcription and Translation Level by MSU-Stimulated Inflammation 48 Summary 53 CONCLUSIONS 54 REFERENCES 56

    1. Anderson, N. L.; Anderson, N. G., The human plasma proteome: history, character, and diagnostic prospects. Molecular & cellular proteomics : MCP 2002, 1 (11), 845-67.
    2. Tyers, M.; Mann, M., From genomics to proteomics. Nature 2003, 422 (6928), 193-7.
    3. Shen, Y.; Jacobs, J. M.; Camp, D. G., 2nd; Fang, R.; Moore, R. J.; Smith, R. D.; Xiao, W.; Davis, R. W.; Tompkins, R. G., Ultra-high-efficiency strong cation exchange LC/RPLC/MS/MS for high dynamic range characterization of the human plasma proteome. Anal Chem 2004, 76 (4), 1134-44.
    4. Harth, G.; Lee, B. Y.; Horwitz, M. A., High-level heterologous expression and secretion in rapidly growing nonpathogenic mycobacteria of four major Mycobacterium tuberculosis extracellular proteins considered to be leading vaccine candidates and drug targets. Infection and immunity 1997, 65 (6), 2321-8.
    5. Ohtsuki, S.; Uchida, Y.; Kubo, Y.; Terasaki, T., Quantitative targeted absolute proteomics-based ADME research as a new path to drug discovery and development: methodology, advantages, strategy, and prospects. J. Pharm. Sci. 2011, 100 (9), 3547-59.
    6. Videau, O.; Delaforge, M.; Levi, M.; Thevenot, E.; Gal, O.; Becquemont, L.; Beaune, P.; Benech, H., Biochemical and analytical development of the CIME cocktail for drug fate assessment in humans. Rapid Commun. Mass Spectrom. 2010, 24 (16), 2407-19.
    7. Gilar, M.; Olivova, P.; Daly, A. E.; Gebler, J. C., Orthogonality of separation in two-dimensional liquid chromatography. Anal Chem 2005, 77 (19), 6426-34.
    8. Delmotte, N.; Lasaosa, M.; Tholey, A.; Heinzle, E.; Huber, C. G., Two-dimensional reversed-phase x ion-pair reversed-phase HPLC: an alternative approach to high-resolution peptide separation for shotgun proteome analysis. J Proteome Res 2007, 6 (11), 4363-73.
    9. Irina Dioumaeva, S.-B. C., Ben Yong, David Jones, Ritu Arora Agilent Technologies, Inc. Understanding Orthogonality in Reversed-Phase Liquid Chromatography for Easier Column Selection and Method Development Application Note [Online], 2010.
    10. Valeja, S. G.; Xiu, L.; Gregorich, Z. R.; Guner, H.; Jin, S.; Ge, Y., Three dimensional liquid chromatography coupling ion exchange chromatography/hydrophobic interaction chromatography/reverse phase chromatography for effective protein separation in top-down proteomics. Anal Chem 2015, 87 (10), 5363-71.
    11. Washburn, M. P.; Wolters, D.; Yates, J. R., 3rd, Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 2001, 19 (3), 242-7.
    12. Buszewski, B.; Noga, S., Hydrophilic interaction liquid chromatography (HILIC)--a powerful separation technique. Analytical and bioanalytical chemistry 2012, 402 (1), 231-47.
    13. Magdeldin, S.; Yamamoto, K.; Yoshida, Y.; Xu, B.; Zhang, Y.; Fujinaka, H.; Yaoita, E.; Yates, J. R., 3rd; Yamamoto, T., Deep proteome mapping of mouse kidney based on OFFGel prefractionation reveals remarkable protein post- translational modifications. J Proteome Res 2014, 13 (3), 1636-46.
    14. Wang, H.; Sun, S.; Zhang, Y.; Chen, S.; Liu, P.; Liu, B., An off-line high pH reversed-phase fractionation and nano-liquid chromatography-mass spectrometry method for global proteomic profiling of cell lines. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2015, 974, 90-5.
    15. Zhou, H.; Dai, J.; Sheng, Q. H.; Li, R. X.; Shieh, C. H.; Guttman, A.; Zeng, R., A fully automated 2-D LC-MS method utilizing online continuous pH and RP gradients for global proteome analysis. Electrophoresis 2007, 28 (23), 4311-4319.
    16. Wolters, D. A.; Washburn, M. P.; Yates, J. R., 3rd, An automated multidimensional protein identification technology for shotgun proteomics. Anal Chem 2001, 73 (23), 5683-90.
    17. Horth, P.; Miller, C. A.; Preckel, T.; Wenz, C., Efficient fractionation and improved protein identification by peptide OFFGEL electrophoresis. Molecular & cellular proteomics : MCP 2006, 5 (10), 1968-74.
    18. Heller, M.; Michel, P. E.; Morier, P.; Crettaz, D.; Wenz, C.; Tissot, J. D.; Reymond, F.; Rossier, J. S., Two-stage Off-Gel isoelectric focusing: protein followed by peptide fractionation and application to proteome analysis of human plasma. Electrophoresis 2005, 26 (6), 1174-88.
    19. Hubner, N. C.; Ren, S.; Mann, M., Peptide separation with immobilized pI strips is an attractive alternative to in-gel protein digestion for proteome analysis. Proteomics 2008, 8 (23-24), 4862-72.
    20. Gilar, M.; Olivova, P.; Daly, A. E.; Gebler, J. C., Two-dimensional separation of peptides using RP-RP-HPLC system with different pH in first and second separation dimensions. J. Sep. Sci. 2005, 28 (14), 1694-1703.
    21. Yang, F.; Shen, Y.; Camp, D. G., 2nd; Smith, R. D., High-pH reversed-phase chromatography with fraction concatenation for 2D proteomic analysis. Expert review of proteomics 2012, 9 (2), 129-34.
    22. Lasaosa, M.; Delmotte, N.; Huber, C. G.; Melchior, K.; Heinzle, E.; Tholey, A., A 2D reversed-phase x ion-pair reversed-phase HPLC-MALDI TOF/TOF-MS approach for shotgun proteome analysis. Analytical and bioanalytical chemistry 2009, 393 (4), 1245-56.
    23. Toll, H.; Oberacher, H.; Swart, R.; Huber, C. G., Separation, detection, and identification of peptides by ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry at high and low pH. J. Chromatogr. A 2005, 1079 (1-2), 274-286.
    24. Alpert, A. J., Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. J. Chromatogr. 1990, 499, 177-96.
    25. Mant, C. T.; Hodges, R. S., Mixed-mode hydrophilic interaction/cation-exchange chromatography (HILIC/CEX) of peptides and proteins. J. Sep. Sci. 2008, 31 (15), 2754-73.
    26. Mauko, L.; Lacher, N. A.; Pelzing, M.; Nordborg, A.; Haddad, P. R.; Hilder, E. F., Comparison of ZIC-HILIC and graphitized carbon-based analytical approaches combined with exoglycosidase digestions for analysis of glycans from monoclonal antibodies. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2012, 911, 93-104.
    27. Gan, C. S.; Guo, T.; Zhang, H.; Lim, S. K.; Sze, S. K., A comparative study of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) versus SCX-IMAC-based methods for phosphopeptide isolation/enrichment. J Proteome Res 2008, 7 (11), 4869-77.
    28. Hao, P.; Guo, T.; Li, X.; Adav, S. S.; Yang, J.; Wei, M.; Sze, S. K., Novel application of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) in shotgun proteomics: comprehensive profiling of rat kidney proteome. J Proteome Res 2010, 9 (7), 3520-6.
    29. O'Farrell, P. H., High resolution two-dimensional electrophoresis of proteins. J. Biol. Chem. 1975, 250 (10), 4007-4021.
    30. Patton, W. F., Detection technologies in proteome analysis. J. Chromatogr. B 2002, 711, 3-31.
    31. Ong, S. E., Blagoev, B., Kratchmarova, I., Kristensen, D.B., Steen, H., Pandey, A., Mann, M., Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics. Mol. Cell Proteomics 2002, 1, 376-386.
    32. Desiderio, D. M.; Kai, M., Preparation of stable isotope-incorporated peptide internal standards for field desorption mass spectrometry quantification of peptides in biologic tissue. Biomed Mass Spectrom 1983, 10 (8), 471-9.
    33. Steven P. Gygi, B. R., Scott A. Gerber, Frantisek Turecek, Michael H. Gelb, Ruedi Aebersold, Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 1999, 17, 6.
    34. Ross, P. L., Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents. Mol. Cell Proteomics 2004, 3 (12), 1154-1169.
    35. Thompson, A., Schäfer, J., Kuhn, K., Kienle, S., Schwarz, J., Schmidt, G., Neumann, T., Johnstone, R., Mohammed, AK., Hamon, C., Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 2003, 75, 1895-904.
    36. Peter Pichler, T. K. c., Johann Holzmann, Michael Mazanek, Thomas Taus, Gustav Ammerer, and Karl Mechtler, Peptide labeling with isobaric tags yields higher identification rates using iTRAQ 4-plex compared to TMT 6-plex and iTRAQ 8-plex on LTQ Orbitrap. Anal. Chem. 2010, 82, 6549–6558.
    37. Ross, P. L.; Huang, Y. N.; Marchese, J. N.; Williamson, B.; Parker, K.; Hattan, S.; Khainovski, N.; Pillai, S.; Dey, S.; Daniels, S.; Purkayastha, S.; Juhasz, P.; Martin, S.; Bartlet-Jones, M.; He, F.; Jacobson, A.; Pappin, D. J., Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Molecular & cellular proteomics : MCP 2004, 3 (12), 1154-69.
    38. Choe, L. H.; Aggarwal, K.; Franck, Z.; Lee, K. H., A comparison of the consistency of proteome quantitation using two-dimensional electrophoresis and shotgun isobaric tagging in Escherichia coli cells. Electrophoresis 2005, 26 (12), 2437-49.
    39. Want, E. J.; Cravatt, B. F.; Siuzdak, G., The expanding role of mass spectrometry in metabolite profiling and characterization. Chembiochem : a European journal of chemical biology 2005, 6 (11), 1941-51.
    40. Schwartz, J. C. S., J. E. P, Quarmby, S. T.Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics. 2005, San Antonio, TX, June 5-9.
    41. B, C., Implementation of multiplexed iTRAQ quantitation tags on ion trap instruments. . Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics 2005, June5-9, San Antonio, Texas
    42. Timothy J. Griffin; Hongwei Xie; Sricharan Bandhakavi; Jonathan Popko; Archana Mohan; John V. Carlis, a. L. H., iTRAQ reagent-based quantitative proteomic analysis on a linear ion trap mass spectrometer. J. Proteome Res. 2007, 6, 4200-4209.
    43. Bantscheff, M.; Boesche, M.; Eberhard, D.; Matthieson, T.; Sweetman, G.; Kuster, B., Robust and sensitive iTRAQ quantification on an LTQ Orbitrap mass spectrometer. Molecular & cellular proteomics : MCP 2008, 7 (9), 1702-13.
    44. AB., G., Observations on certain pathological conditions of the blood and urine, in gout, rheumatism, and Bright's disease. Med Chir Trans 1848, 83-97.
    45. McCarty, D. J.; Hollander, J. L., Identification of urate crystals in gouty synovial fluid. Ann Intern Med 1961, 54, 452-60.
    46. Cronstein, B. N.; Terkeltaub, R., The inflammatory process of gout and its treatment. Arthritis Res. Ther. 2006, 8 Suppl 1, S3.
    47. Edwards, J. C.; Sedgwick, A. D.; Willoughby, D. A., The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J Pathol 1981, 134 (2), 147-56.
    48. Pessler, F., Mayer, C. T., Jung, S. M., Behrens, E. M., Dai, L., Menetski, J. P., Schumacher, H. R., Identification of novel monosodium urate crystal regulated mRNAs by transcript profiling of dissected murine air pouch membranes. Arthritis Res. Ther. 2008, 10 (3), R64.
    49. Jung, S. M., Schumacher, H. R., Kim, H., Kim, M., Lee, S. H., Pessler, F., Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels. Arthritis Res. Ther. 2007, 9 (4), R64.
    50. Schwanhausser, B.; Busse, D.; Li, N.; Dittmar, G.; Schuchhardt, J.; Wolf, J.; Chen, W.; Selbach, M., Global quantification of mammalian gene expression control. Nature 2011, 473 (7347), 337-42.
    51. Slebos, R. J., Brock, J.W., Winters, N.F., Stuart, S.R., Martinez, M.A., Li, M., Chambers, M.C., Zimmerman, L.J., Ham, A.J., Tabb, D.L., Liebler, D.C., Evaluation of Strong Cation Exchange versus Isoelectric Focusing of Peptides for Multidimensional Liquid Chromatography-Tandem Mass Spectrometry. J. Proteome Res. 2008, 7, 9.
    52. Ko, C. H.; Cheng, C. F.; Lai, C. P.; Tzu, T. H.; Chiu, C. W.; Lin, M. W.; Wu, S. Y.; Sun, C. Y.; Tseng, H. W.; Wang, C. C.; Kuo, Z. K.; Wang, L. M.; Chen, S. F., Differential proteomic analysis of cancer stem cell properties in hepatocellular carcinomas by isobaric tag labeling and mass spectrometry. J Proteome Res 2013, 12 (8), 3573-85.
    53. Armenta, J. M.; Hoeschele, I.; Lazar, I. M., Differential protein expression analysis using stable isotope labeling and PQD linear ion trap MS technology. J. Am. Soc. Mass. Spectrom. 2009, 20 (7), 1287-302.
    54. Chee Sian Gan, T. G., Huoming Zhang, Sai Kiang Lim, and Siu Kwan Sze, A Comparative Study of Electrostatic Repulsion-Hydrophilic Interaction Chromatography (ERLIC) versus SCX-IMAC-Based Methods for Phosphopeptide Isolation/Enrichment. J Proteome Res 2008, 7, 4869–4877.
    55. Junmin Peng, J. E. E., Carson C. Thoreen, Larry J. Licklider and Steven P. Gygi, Evaluation of Multidimensional Chromatography Coupled with Tandem Mass Spectrometry (LC/LC-MS/MS) for Large-Scale Protein Analysis The Yeast Proteome. J Proteome Res 2003, 2, 43-50.
    56. Chenau, J.; Michelland, S.; Sidibe, J.; Seve, M., Peptides OFFGEL electrophoresis: a suitable pre-analytical step for complex eukaryotic samples fractionation compatible with quantitative iTRAQ labeling. Proteome science 2008, 6 (1), 9.
    57. Gilar, M.; Jaworski, A., Retention behavior of peptides in hydrophilic-interaction chromatography. J. Chromatogr. A 2011, 1218 (49), 8890-6.
    58. Bryan A. Ballif, J. V. n., Sean A. Beausoleil, Daniel Schwartz, and Steven P. Gygi, Phosphoproteomic Analysis of the Developing Mouse Brain. Mol. Cell Proteomics 2004, 3 (11), 1093-1101.
    59. Kyte, J.; Doolittle, R. F., A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 1982, 157 (1), 105-32.
    60. Hoang-Trang Lam, J. J., Niels Lion, and H. H. Girault, Modeling the Isoelectric Focusing of Peptides in an OFFGEL Multicompartment Cell. J Proteome Res 2007, 6, 1666-1676.
    61. Volmer, L. S. a. D. A., Ion activation methods for tandem mass spectrometry. J. Mass Spectrom. 2004, 39 (10), 1091-112.
    62. So, A., Gout in the spotlight. Arthritis Res Ther 2008, 10 (3), 112.
    63. Wang, H.; Chang-Wong, T.; Tang, H. Y.; Speicher, D. W., Comparison of extensive protein fractionation and repetitive LC-MS/MS analyses on depth of analysis for complex proteomes. J Proteome Res 2010, 9 (2), 1032-40.
    64. Doherty, M., Whicher, J.T., Dieppe, P.A. , Activation of the alternative pathway of complement by monosodium urate monohydrate crystals and other inflammatory particles. Ann. Rheum. Dis. 1983, 42, 285-291.
    65. Rodriguez de Cordoba, S.; Esparza-Gordillo, J.; Goicoechea de Jorge, E.; Lopez-Trascasa, M.; Sanchez-Corral, P., The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 2004, 41 (4), 355-67.
    66. Umemoto, T.; Han, C. Y.; Mitra, P.; Averill, M. M.; Tang, C.; Goodspeed, L.; Omer, M.; Subramanian, S.; Wang, S.; Den Hartigh, L. J.; Wei, H.; Kim, E. J.; Kim, J.; O'Brien, K. D.; Chait, A., Apolipoprotein AI and high-density lipoprotein have anti-inflammatory effects on adipocytes via cholesterol transporters: ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1. Circ Res 2013, 112 (10), 1345-54.
    67. Cheung, M. C.; Brown, B. G.; Marino Larsen, E. K.; Frutkin, A. D.; O'Brien, K. D.; Albers, J. J., Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease. Biochim. Biophys. Acta 2006, 1762 (1), 131-7.
    68. Altieri, D. C.; Plescia, J.; Plow, E. F., The structural motif glycine 190-valine 202 of the fibrinogen gamma chain interacts with CD11b/CD18 integrin (alpha M beta 2, Mac-1) and promotes leukocyte adhesion. J. Biol. Chem. 1993, 268 (3), 1847-53.
    69. Simard, J. C.; Cesaro, A.; Chapeton-Montes, J.; Tardif, M.; Antoine, F.; Girard, D.; Tessier, P. A., S100A8 and S100A9 induce cytokine expression and regulate the NLRP3 inflammasome via ROS-dependent activation of NF-kappaB. PLoS ONE 2013, 8 (8), 12.
    70. Martinon, F.; Petrilli, V.; Mayor, A.; Tardivel, A.; Tschopp, J., Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006, 440 (7081), 237-41.
    71. Chen, C. J.; Shi, Y.; Hearn, A.; Fitzgerald, K.; Golenbock, D.; Reed, G.; Akira, S.; Rock, K. L., MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 2006, 116 (8), 2262-71.
    72. Auvynet, C.; Rosenstein, Y., Multifunctional host defense peptides: antimicrobial peptides, the small yet big players in innate and adaptive immunity. FEBS J 2009, 276 (22), 6497-508.
    73. Kahlenberg, J. M.; Carmona-Rivera, C.; Smith, C. K.; Kaplan, M. J., Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages. J Immunol 2013, 190 (3), 1217-26.
    74. Mills, E.; O'Neill, L. A., Succinate: a metabolic signal in inflammation. Trends Cell Biol 2014, 24 (5), 313-20.
    75. Infantino, V. C., P.; Cucci, L.; Panaro, M. A.; Di Noia, M. A.; Calvello, R.; Palmieri, F.; Iacobazzi, V., The mitochondrial citrate carrier: a new player in inflammation. Biochem. J 2011, 438 (3), 433-6.
    76. Tannahill, G. M.; Curtis, A. M.; Adamik, J.; Palsson-McDermott, E. M.; McGettrick, A. F.; Goel, G.; Frezza, C.; Bernard, N. J.; Kelly, B.; Foley, N. H.; Zheng, L.; Gardet, A.; Tong, Z.; Jany, S. S.; Corr, S. C.; Haneklaus, M.; Caffrey, B. E.; Pierce, K.; Walmsley, S.; Beasley, F. C.; Cummins, E.; Nizet, V.; Whyte, M.; Taylor, C. T.; Lin, H.; Masters, S. L.; Gottlieb, E.; Kelly, V. P.; Clish, C.; Auron, P. E.; Xavier, R. J.; O'Neill, L. A., Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 2013, 496 (7444), 238-42.
    77. He, W.; Newman, J. C.; Wang, M. Z.; Ho, L.; Verdin, E., Mitochondrial sirtuins: regulators of protein acylation and metabolism. Trends in endocrinology and metabolism: TEM 2012, 23 (9), 467-76.
    78. Liu, T. F.; McCall, C. E., Deacetylation by SIRT1 Reprograms Inflammation and Cancer. Genes cancer 2013, 4 (3-4), 135-47.
    79. Misawa, T., Takahama, M., Kozaki, T., Lee, H., Zou, J., Saitoh, T., Akira, S., Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome. Nat. Immunol. 2013, 14, 454–460.
    80. Schug, T. T. X., Q.; Gao, H.; Peres-da-Silva, A.; Draper, D. W.; Fessler, M. B.; Purushotham, A.; Li, X.;, Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol Cell Biol 2010, 30 (19), 4712-21.
    81. Garedew, A., Henderson, S. O., Moncada, S., Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death. Cell Death Differ. 2010, 17, 1540-1550.
    82. Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., Pearce, E. J., Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation. Blood 2010, 115 (23), 4742-4749.
    83. Rodríguez-Prados, J. C., Través, P. G., Cuenca, J., Rico, D., Aragonés, J., Martín-Sanz, P., Cascante, M., Boscá, L., Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol 2010, 185 (1), 605-14.
    84. Mills, C. D., M1 and M2 Macrophages: Oracles of Health and Disease. Crit Rev Immunol 2012, 32 (6), 463-88.
    85. Martin, W. J.; Shaw, O.; Liu, X.; Steiger, S.; Harper, J. L., Monosodium urate monohydrate crystal-recruited noninflammatory monocytes differentiate into M1-like proinflammatory macrophages in a peritoneal murine model of gout. Arthritis Rheum 2011, 63 (5), 1322-32.
    86. Jitrapakdee, S., St Maurice, M., Rayment, I., Cleland, W. W., Wallace, J. C., Attwood, P.V., Structure, mechanism and regulation of pyruvate carboxylase. Biochem. J 2008, 413 (3), 369-87.
    87. Li, X., Ren, Y., Sorokin, V., Poh, K. K., Ho, H. H., Lee, C. N., de Kleijn, D., Lim, S. K., Tam, J. P., Sze, S. K., Quantitative profiling of the rat heart myoblast secretome reveals differential responses to hypoxia and re-oxygenation stress. J. Proteomics 2014, 98, 138-49.

    下載圖示
    QR CODE