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研究生:陳素慧
研究生(外文):CHEN, SU-HUEI
論文名稱:硬膜上壓迫造成血腦屏障受損的分子機制
論文名稱(外文):Molecular mechanism underlying disruption of blood-brain barrier caused by epidural compression
指導教授:劉培新劉培新引用關係
指導教授(外文):LIU, PEI-HSIN
口試委員:林嘉志袁宗凡
口試委員(外文):LIN, CHIA-CHIHYUAN, ZUNG-FAN
口試日期:2017-12-29
學位類別:碩士
校院名稱:慈濟大學
系所名稱:生理暨解剖醫學碩士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:中文
論文頁數:41
中文關鍵詞:硬膜上壓迫主要體感覺皮質血腦屏障緊密連接泛素
外文關鍵詞:epidural compressionprimary somatosensory cortexblood-brain barriertight junctionubiquitin
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我們先前報導,大鼠主要體感覺皮質受硬膜上壓迫會造成短期的腦微血管血腦屏障受損,給予抗氧化劑可避免血腦屏障受損,但其機制仍然未知。In vitro研究顯示,血腦屏障的通透性是由內皮細胞tight junction (TJ) proteins的磷酸化、泛素化及後續的重分布來調控。因此,我們假設主要體感覺皮質受硬膜上壓迫傷害血腦屏障是經由改變TJ proteins磷酸化、泛素化及後續重分布的調節。免疫轉漬實驗結果顯示,主要體感覺皮質受壓迫三天,TJ proteins claudin-5、occludin及JAM-1的表現量不變,但此時血腦屏障受損。給予抗氧化劑增加了claudin-5的表現量,但不增加occludin及JAM-1的表現量。接著,免疫沉降及分餾分析實驗結果顯示,主要體感覺皮質受壓迫三天造成claudin-5 在 cytosol及membrane fraction的磷酸化及泛素化增加。給予抗氧化劑ascorbic acid不但減低了claudin-5的磷酸化及泛素化,也大幅增加了claudin-5 在 membrane fraction的表現量。許多攜帶蛋白例如Epsin1、Eps15及Hrs已確知會負責membrane proteins的endocytosis及intracellular trafficking。因此,我們研究且發現主要體感覺皮質受壓迫造成claudin-5與Epsin1、Eps15及Hrs的作用增加。給予ascorbic acid只減少claudin-5與Epsin1及Eps15的作用,但不減少與Hrs的作用。綜合以上,我們的實驗結果顯示,主要體感覺皮質受硬膜上壓迫傷害血腦屏障是經由claudin-5的磷酸化、泛素化及後續的重分布,ascorbic acid可能可應用在硬膜上壓迫併發血腦屏障受損的治療。
We previously reported that epidural compression of the rat primary somatosensory cortex leads to short-term breakdown of the blood-brain barrier (BBB) of cerebral microvessels, which is prevented by the treatment of antioxidants. However, the underlying mechanism remains unknown. In vitro studies have shown that the permeability of BBB is regulated by the phosphorylation, ubiquitination, and then redistribution of tight junction (TJ) proteins in the endothelial cells. Thus, we hypothesized that epidural compression of the primary somatosensory cortex impairs the BBB through alterations of the regulation of phosphorylation, ubiquitination, and then redistribution of TJ proteins. Immunoblotting demonstrated that the expressions of TJ proteins claudin-5, occludin, and JAM-1 were unaltered at 3 days post-compression when the BBB was disrupted. Treatment of antioxidants increased the expression of claudin-5 but not occludin and JAM-1. Next, immunoprecipitation and fractional analysis showed that 3-day-compression elevated the phosphorylation and ubiquitination of claudin-5 both in the cytosol and membrane fractions. Treatment of ascorbic acid not only reduced the phosphorylation and ubiquitination of claudin-5 but also dramatically increased the expression of claudin-5 in the membrane fraction. A number of carrier proteins such as Epsin1, Eps15, and Hrs are well-known to be responsible for the endocytosis and intracellular trafficking of membrane proteins. Thus, we examined and found that the interaction of claudin-5 with Epsin1, Eps15, and Hrs was increased post-compression. Treatment of ascorbic acid only reduced the interaction of claudin-5 with Epsin1 and Eps15 but not Hrs. Together, these data suggest that epidural compression of the rat primary somatosensory cortex compromises the BBB integrity through phosphorylation, ubiquitination, and redistribution of claudin-5. Ascorbic acid may be used therapeutically to modulate epidural compression complicated with BBB dysfunction.
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中文摘要------------------------03
引言----------------------------04
材料與方法----------------------10
結果----------------------------14
討論----------------------------18
結論----------------------------22
參考文獻------------------------23
圖片與說明----------------------32
Abramov, A.Y., Scorziello, A. & Duchen, M.R. (2007) Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation. J Neurosci, 27, 1129-1138.
Andras, I.E., Deli, M.A., Veszelka, S., Hayashi, K., Hennig, B. & Toborek, M. (2007) The NMDA and AMPA/KA receptors are involved in glutamate-induced alterations of occludin expression and phosphorylation in brain endothelial cells. J Cereb Blood Flow Metab, 27, 1431-1443.
Andreeva, A.Y., Krause, E., Muller, E.C., Blasig, I.E. & Utepbergenov, D.I. (2001) Protein kinase C regulates the phosphorylation and cellular localization of occludin. The Journal of biological chemistry, 276, 38480-38486.
Beckman, J.S. & Koppenol, W.H. (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. The American journal of physiology, 271, C1424-1437.
Boje, K.M. & Lakhman, S.S. (2000) Nitric oxide redox species exert differential permeability effects on the blood-brain barrier. J Pharmacol Exp Ther, 293, 545-550.
Brennan, A.M., Suh, S.W., Won, S.J., Narasimhan, P., Kauppinen, T.M., Lee, H., Edling, Y., Chan, P.H. & Swanson, R.A. (2009) NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci, 12, 857-863.
Bricolo, A.P. & Pasut, L.M. (1984) Extradural hematoma: toward zero mortality. A prospective study. Neurosurgery, 14, 8-12.
Burnett, M.G., Detre, J.A. & Greenberg, J.H. (2005) Activation-flow coupling during graded cerebral ischemia. Brain Res, 1047, 112-118.
Chen, H. & De Camilli, P. (2005) The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin. Proceedings of the National Academy of Sciences of the United States of America, 102, 2766-2771.
Chen, H., Fre, S., Slepnev, V.I., Capua, M.R., Takei, K., Butler, M.H., Di Fiore, P.P. & De Camilli, P. (1998) Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature, 394, 793-797.
Chen, H., Song, Y.S. & Chan, P.H. (2009) Inhibition of NADPH oxidase is neuroprotective after ischemia-reperfusion. J Cereb Blood Flow Metab, 29, 1262-1272.
Chen, J.R., Wang, Y.J. & Tseng, G.F. (2003) The effect of epidural compression on cerebral cortex: a rat model. Journal of neurotrauma, 20, 767-780.
Clarke, H., Soler, A.P. & Mullin, J.M. (2000) Protein kinase C activation leads to dephosphorylation of occludin and tight junction permeability increase in LLC-PK1 epithelial cell sheets. Journal of cell science, 113 ( Pt 18), 3187-3196.
Cordobes, F., Lobato, R.D., Rivas, J.J., Munoz, M.J., Chillon, D., Portillo, J.M. & Lamas, E. (1981) Observations on 82 patients with extradural hematoma. Comparison of results before and after the advent of computerized tomography. J Neurosurg, 54, 179-186.
DeAngelis, L.M. (2001) Brain tumors. N Engl J Med, 344, 114-123.
Di Fiore, P.P., Polo, S. & Hofmann, K. (2003) When ubiquitin meets ubiquitin receptors: a signalling connection. Nat Rev Mol Cell Biol, 4, 491-497.
Duval, M., Bedard-Goulet, S., Delisle, C. & Gratton, J.P. (2003) Vascular endothelial growth factor-dependent down-regulation of Flk-1/KDR involves Cbl-mediated ubiquitination. Consequences on nitric oxide production from endothelial cells. The Journal of biological chemistry, 278, 20091-20097.
Elias, B.C., Suzuki, T., Seth, A., Giorgianni, F., Kale, G., Shen, L., Turner, J.R., Naren, A., Desiderio, D.M. & Rao, R. (2009) Phosphorylation of Tyr-398 and Tyr-402 in occludin prevents its interaction with ZO-1 and destabilizes its assembly at the tight junctions. The Journal of biological chemistry, 284, 1559-1569.
Farshori, P. & Kachar, B. (1999) Redistribution and phosphorylation of occludin during opening and resealing of tight junctions in cultured epithelial cells. The Journal of membrane biology, 170, 147-156.
Fazioli, F., Minichiello, L., Matoskova, B., Wong, W.T. & Di Fiore, P.P. (1993) eps15, a novel tyrosine kinase substrate, exhibits transforming activity. Mol Cell Biol, 13, 5814-5828.
Ford, M.G., Mills, I.G., Peter, B.J., Vallis, Y., Praefcke, G.J., Evans, P.R. & McMahon, H.T. (2002) Curvature of clathrin-coated pits driven by epsin. Nature, 419, 361-366.
Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S. & Tsukita, S. (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol, 123, 1777-1788.
Girouard, H., Wang, G., Gallo, E.F., Anrather, J., Zhou, P., Pickel, V.M. & Iadecola, C. (2009) NMDA receptor activation increases free radical production through nitric oxide and NOX2. J Neurosci, 29, 2545-2552.
Gonzalez-Mariscal, L., Tapia, R. & Chamorro, D. (2008) Crosstalk of tight junction components with signaling pathways. Biochimica et biophysica acta, 1778, 729-756.
Guillemot, L., Paschoud, S., Pulimeno, P., Foglia, A. & Citi, S. (2008) The cytoplasmic plaque of tight junctions: a scaffolding and signalling center. Biochimica et biophysica acta, 1778, 601-613.
Haorah, J., Heilman, D., Knipe, B., Chrastil, J., Leibhart, J., Ghorpade, A., Miller, D.W. & Persidsky, Y. (2005) Ethanol-induced activation of myosin light chain kinase leads to dysfunction of tight junctions and blood-brain barrier compromise. Alcoholism, clinical and experimental research, 29, 999-1009.
Haorah, J., Ramirez, S.H., Schall, K., Smith, D., Pandya, R. & Persidsky, Y. (2007) Oxidative stress activates protein tyrosine kinase and matrix metalloproteinases leading to blood-brain barrier dysfunction. Journal of neurochemistry, 101, 566-576.
Hawkins, B.T. & Davis, T.P. (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacological reviews, 57, 173-185.
Hershko, A. & Ciechanover, A. (1998) The ubiquitin system. Annual review of biochemistry, 67, 425-479.
Hicke, L. (2001) A new ticket for entry into budding vesicles-ubiquitin. Cell, 106, 527-530.
Huang, F., Kirkpatrick, D., Jiang, X., Gygi, S. & Sorkin, A. (2006) Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell, 21, 737-748.
Inamura, A., Adachi, Y., Inoue, T., He, Y., Tokuda, N., Nawata, T., Shirao, S., Nomura, S., Fujii, M., Ikeda, E., Owada, Y. & Suzuki, M. (2013) Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5. Neurochem Res, 38, 1641-1647.
Inskip, P.D., Mellemkjaer, L., Gridley, G. & Olsen, J.H. (1998) Incidence of intracranial tumors following hospitalization for head injuries (Denmark). Cancer Causes Control, 9, 109-116.
Inskip, P.D., Tarone, R.E., Hatch, E.E., Wilcosky, T.C., Shapiro, W.R., Selker, R.G., Fine, H.A., Black, P.M., Loeffler, J.S. & Linet, M.S. (2001) Cellular-telephone use and brain tumors. N Engl J Med, 344, 79-86.
Ivanov, A.I., Nusrat, A. & Parkos, C.A. (2004) Endocytosis of epithelial apical junctional proteins by a clathrin-mediated pathway into a unique storage compartment. Mol Biol Cell, 15, 176-188.
Kacem, K., Lacombe, P., Seylaz, J. & Bonvento, G. (1998) Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia, 23, 1-10.
Komada, M. & Kitamura, N. (2001) Hrs and hbp: possible regulators of endocytosis and exocytosis. Biochem Biophys Res Commun, 281, 1065-1069.
Komada, M., Masaki, R., Yamamoto, A. & Kitamura, N. (1997) Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes. The Journal of biological chemistry, 272, 20538-20544.
Kuhlmann, C.R., Lessmann, V. & Luhmann, H.J. (2006) Fluvastatin stabilizes the blood-brain barrier in vitro by nitric oxide-dependent dephosphorylation of myosin light chains. Neuropharmacology, 51, 907-913.
Kundrotiene, J., Wagner, A. & Liljequist, S. (2002) Extradural compression of sensorimotor cortex: a useful model for studies on ischemic brain damage and neuroprotection. Journal of neurotrauma, 19, 69-84.
Leclair, H.M., Andre-Gregoire, G., Treps, L., Azzi, S., Bidere, N. & Gavard, J. (2016) The E3 ubiquitin ligase MARCH3 controls the endothelial barrier. FEBS letters, 590, 3660-3668.
Lee, E.J., Hung, Y.C., Wang, L.C., Chung, K.C. & Chen, H.H. (1998) Factors influencing the functional outcome of patients with acute epidural hematomas: analysis of 200 patients undergoing surgery. J Trauma, 45, 946-952.
Lee, H.S., Namkoong, K., Kim, D.H., Kim, K.J., Cheong, Y.H., Kim, S.S., Lee, W.B. & Kim, K.Y. (2004) Hydrogen peroxide-induced alterations of tight junction proteins in bovine brain microvascular endothelial cells. Microvasc Res, 68, 231-238.
Lewen, A., Matz, P. & Chan, P.H. (2000) Free radical pathways in CNS injury. J Neurotrauma, 17, 871-890.
Lin, J.L., Huang, Y.H., Shen, Y.C., Huang, H.C. & Liu, P.H. (2010) Ascorbic acid prevents blood-brain barrier disruption and sensory deficit caused by sustained compression of primary somatosensory cortex. J Cereb Blood Flow Metab, 30, 1121-1136.
Lipton, S.A., Choi, Y.B., Pan, Z.H., Lei, S.Z., Chen, H.S., Sucher, N.J., Loscalzo, J., Singel, D.J. & Stamler, J.S. (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 364, 626-632.
Lui, W.Y. & Lee, W.M. (2005) cAMP perturbs inter-Sertoli tight junction permeability barrier in vitro via its effect on proteasome-sensitive ubiquitination of occludin. Journal of cellular physiology, 203, 564-572.
Mandel, I., Paperna, T., Volkowich, A., Merhav, M., Glass-Marmor, L. & Miller, A. (2012) The ubiquitin-proteasome pathway regulates claudin 5 degradation. J Cell Biochem, 113, 2415-2423.
Martin-Padura, I., Lostaglio, S., Schneemann, M., Williams, L., Romano, M., Fruscella, P., Panzeri, C., Stoppacciaro, A., Ruco, L., Villa, A., Simmons, D. & Dejana, E. (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol, 142, 117-127.
Matsuda, M., Kubo, A., Furuse, M. & Tsukita, S. (2004) A peculiar internalization of claudins, tight junction-specific adhesion molecules, during the intercellular movement of epithelial cells. J Cell Sci, 117, 1247-1257.
Mayer, S.A. & Rincon, F. (2005) Treatment of intracerebral haemorrhage. Lancet Neurol, 4, 662-672.
McCord, J.M. (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med, 312, 159-163.
Mertsch, K., Blasig, I. & Grune, T. (2001) 4-Hydroxynonenal impairs the permeability of an in vitro rat blood-brain barrier. Neurosci Lett, 314, 135-138.
Mohanty, A., Kolluri, V.R., Subbakrishna, D.K., Satish, S., Mouli, B.A. & Das, B.S. (1995) Prognosis of extradural haematomas in children. Pediatr Neurosurg, 23, 57-63.
Morita, K., Furuse, M., Fujimoto, K. & Tsukita, S. (1999) Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proceedings of the National Academy of Sciences of the United States of America, 96, 511-516.
Muellner, A., Benz, M., Kloss, C.U., Mautes, A., Burggraf, D. & Hamann, G.F. (2003) Microvascular basal lamina antigen loss after traumatic brain injury in the rat. Journal of neurotrauma, 20, 745-754.
Mullin, J.M., Marano, C.W., Laughlin, K.V., Nuciglio, M., Stevenson, B.R. & Soler, P. (1997) Different size limitations for increased transepithelial paracellular solute flux across phorbol ester and tumor necrosis factor-treated epithelial cell sheets. Journal of cellular physiology, 171, 226-233.
Murakami, T., Felinski, E.A. & Antonetti, D.A. (2009) Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor-induced permeability. The Journal of biological chemistry, 284, 21036-21046.
Nitta, T., Hata, M., Gotoh, S., Seo, Y., Sasaki, H., Hashimoto, N., Furuse, M. & Tsukita, S. (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol, 161, 653-660.
Ohtsuki, S., Sato, S., Yamaguchi, H., Kamoi, M., Asashima, T. & Terasaki, T. (2007) Exogenous expression of claudin-5 induces barrier properties in cultured rat brain capillary endothelial cells. J Cell Physiol, 210, 81-86.
Ozaki, H., Ishii, K., Horiuchi, H., Arai, H., Kawamoto, T., Okawa, K., Iwamatsu, A. & Kita, T. (1999) Cutting edge: combined treatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells. J Immunol, 163, 553-557.
Parathath, S.R., Parathath, S. & Tsirka, S.E. (2006) Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier in tPA-dependent excitotoxic injury in mice. J Cell Sci, 119, 339-349.
Parks, D.A. & Granger, D.N. (1986) Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand Suppl, 548, 87-99.
Pollak, L., Walach, N., Gur, R. & Schiffer, J. (1998) Meningiomas after radiotherapy for tinea capitis--still no history. Tumori, 84, 65-68.
Raiborg, C., Bache, K.G., Gillooly, D.J., Madshus, I.H., Stang, E. & Stenmark, H. (2002) Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nat Cell Biol, 4, 394-398.
Rao, R.K., Basuroy, S., Rao, V.U., Karnaky Jr, K.J. & Gupta, A. (2002) Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress. Biochem J, 368, 471-481.
Rochfort, K.D., Collins, L.E., McLoughlin, A. & Cummins, P.M. (2015) Shear-dependent attenuation of cellular ROS levels can suppress proinflammatory cytokine injury to human brain microvascular endothelial barrier properties. J Cereb Blood Flow Metab, 35, 1648-1656.
Salvatore, J.R., Weitberg, A.B. & Mehta, S. (1996) Nonionizing electromagnetic fields and cancer: a review. Oncology (Williston Park), 10, 563-570; discussion 573-564, 577-568.
Scholler, K., Trinkl, A., Klopotowski, M., Thal, S.C., Plesnila, N., Trabold, R., Hamann, G.F., Schmid-Elsaesser, R. & Zausinger, S. (2007) Characterization of microvascular basal lamina damage and blood-brain barrier dysfunction following subarachnoid hemorrhage in rats. Brain Res, 1142, 237-246.
Schreibelt, G., Kooij, G., Reijerkerk, A., van Doorn, R., Gringhuis, S.I., van der Pol, S., Weksler, B.B., Romero, I.A., Couraud, P.O., Piontek, J., Blasig, I.E., Dijkstra, C.D., Ronken, E. & de Vries, H.E. (2007) Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling. FASEB J, 21, 3666-3676.
Shen, L. & Turner, J.R. (2005) Actin depolymerization disrupts tight junctions via caveolae-mediated endocytosis. Mol Biol Cell, 16, 3919-3936.
Shen, W., Li, S., Chung, S.H., Zhu, L., Stayt, J., Su, T., Couraud, P.O., Romero, I.A., Weksler, B. & Gillies, M.C. (2011) Tyrosine phosphorylation of VE-cadherin and claudin-5 is associated with TGF-beta1-induced permeability of centrally derived vascular endothelium. Eur J Cell Biol, 90, 323-332.
Sheth, P., Basuroy, S., Li, C., Naren, A.P. & Rao, R.K. (2003) Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions. The Journal of biological chemistry, 278, 49239-49245.
Sims, N.R. & Anderson, M.F. (2002) Mitochondrial contributions to tissue damage in stroke. Neurochem Int, 40, 511-526.
Soma, T., Chiba, H., Kato-Mori, Y., Wada, T., Yamashita, T., Kojima, T. & Sawada, N. (2004) Thr(207) of claudin-5 is involved in size-selective loosening of the endothelial barrier by cyclic AMP. Experimental cell research, 300, 202-212.
Stamatovic, S.M., Dimitrijevic, O.B., Keep, R.F. & Andjelkovic, A.V. (2006) Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain endothelial permeability. The Journal of biological chemistry, 281, 8379-8388.
Stamatovic, S.M., Keep, R.F., Wang, M.M., Jankovic, I. & Andjelkovic, A.V. (2009) Caveolae-mediated internalization of occludin and claudin-5 during CCL2-induced tight junction remodeling in brain endothelial cells. The Journal of biological chemistry, 284, 19053-19066.
Staub, O. & Rotin, D. (2006) Role of ubiquitylation in cellular membrane transport. Physiol Rev, 86, 669-707.
Takahashi, S., Iwamoto, N., Sasaki, H., Ohashi, M., Oda, Y., Tsukita, S. & Furuse, M. (2009) The E3 ubiquitin ligase LNX1p80 promotes the removal of claudins from tight junctions in MDCK cells. J Cell Sci, 122, 985-994.
Traweger, A., Fang, D., Liu, Y.C., Stelzhammer, W., Krizbai, I.A., Fresser, F., Bauer, H.C. & Bauer, H. (2002) The tight junction-specific protein occludin is a functional target of the E3 ubiquitin-protein ligase itch. The Journal of biological chemistry, 277, 10201-10208.
Tsujimoto, S., Pelto-Huikko, M., Aitola, M., Meister, B., Vik-Mo, E.O., Davanger, S., Scheller, R.H. & Bean, A.J. (1999) The cellular and developmental expression of hrs-2 in rat. The European journal of neuroscience, 11, 3047-3063.
van Bergen En Henegouwen, P.M. (2009) Eps15: a multifunctional adaptor protein regulating intracellular trafficking. Cell Commun Signal, 7, 24.
Walter, A.W., Hancock, M.L., Pui, C.H., Hudson, M.M., Ochs, J.S., Rivera, G.K., Pratt, C.B., Boyett, J.M. & Kun, L.E. (1998) Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital. J Clin Oncol, 16, 3761-3767.
Weissman, A.M., Shabek, N. & Ciechanover, A. (2011) The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation. Nat Rev Mol Cell Biol, 12, 605-620.
Wendland, B. (2002) Epsins: adaptors in endocytosis? Nat Rev Mol Cell Biol, 3, 971-977.
Wendland, B., Steece, K.E. & Emr, S.D. (1999) Yeast epsins contain an essential N-terminal ENTH domain, bind clathrin and are required for endocytosis. EMBO J, 18, 4383-4393.
Wester, K. (1999) Decompressive surgery for "pure" epidural hematomas: does neurosurgical expertise improve the outcome? Neurosurgery, 44, 495-500; discussion 500-492.
Wong, D., Dorovini-Zis, K. & Vincent, S.R. (2004) Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood-brain barrier. Experimental neurology, 190, 446-455.
Wosik, K., Cayrol, R., Dodelet-Devillers, A., Berthelet, F., Bernard, M., Moumdjian, R., Bouthillier, A., Reudelhuber, T.L. & Prat, A. (2007) Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis. J Neurosci, 27, 9032-9042.
Yamamoto, M., Ramirez, S.H., Sato, S., Kiyota, T., Cerny, R.L., Kaibuchi, K., Persidsky, Y. & Ikezu, T. (2008) Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells. Am J Pathol, 172, 521-533.
Yang, Y., Estrada, E.Y., Thompson, J.F., Liu, W. & Rosenberg, G.A. (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab, 27, 697-709.
Zhao, J., Moore, A.N., Redell, J.B. & Dash, P.K. (2007) Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci, 27, 10240-10248.
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