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Licensed Unlicensed Requires Authentication Published by De Gruyter February 6, 2014

Role of caveolin-1 in the biology of the blood-brain barrier

  • Yong-Lin Zhao

    Yong-Lin Zhao is working on his PhD degree with Jin-Ning Song as his supervisor. He uses a wide range of biochemical and molecular biological techniques to decipher mechanisms of delayed neuronal death after stroke. Zhao’s research interests include understanding how TRP channels regulate cellular physiology and pathophysiology after ischemia. He currently focuses on the effect of caveola in the regulation of transient receptor potential channels.

    , Jin-Ning Song

    Jin-Ning Song, who is a Professor at Xi’an Jiaotong University, has worked in the Department of Neurosurgery for over 20 years. He has vast experience in the diagnosis and treatment of cerebrovascular diseases, brain tumors and traumatic brain injuries. Song is also one of the main researchers in China whose research interests include the clinical and fundamental studies of cerebrovascular diseases and brain injuries, especially in subarachnoid hemorrhage and diffuse axonal injury.

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    and Ming Zhang

    Ming Zhang, whose medical training culminated with a doctorate in Neurosurgery in Xi’an Jiaotong University, worked on store-operated calcium channels and mammalian TRP channels after stroke with Jin-Ning Song, and currently focuses on functional properties and regulation of ion transport mechanisms in subarachnoid hemorrhage and cerebral ischemia.

Abstract

Caveolin-1 is the principal marker of caveolae in endothelial cells. It plays an important role in physiological and pathological conditions of the blood-brain barrier and serves as a mediator in drug delivery through the blood-brain barrier. Caveolin-1 is related to the diminished expression of tight junction-associated proteins and metabolic pinocytosis vesicles when the blood-brain barrier is destroyed by outside invaders or malignant stimulus. The permeability of the blood-brain barrier, regulated by types of drugs or physical irradiation, is connected with drug transportation with the participation of caveolin-1. Caveolin-1, which serves as a platform or medium for signal transduction, cooperates with several signal molecules by forming a complex. Silencing of caveolin-1 and disruption of caveolae can attenuate or remove pathological damage and even engender the opposite effects in the blood-brain barrier. This review considers the role of caveolin-1 in the blood-brain barrier that may have profound implications for central nervous system disease and drug delivery through the blood-brain barrier.


Corresponding author: Jin-Ning Song, Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, Shaanxi 710061, China, e-mail:

About the authors

Yong-Lin Zhao

Yong-Lin Zhao is working on his PhD degree with Jin-Ning Song as his supervisor. He uses a wide range of biochemical and molecular biological techniques to decipher mechanisms of delayed neuronal death after stroke. Zhao’s research interests include understanding how TRP channels regulate cellular physiology and pathophysiology after ischemia. He currently focuses on the effect of caveola in the regulation of transient receptor potential channels.

Jin-Ning Song

Jin-Ning Song, who is a Professor at Xi’an Jiaotong University, has worked in the Department of Neurosurgery for over 20 years. He has vast experience in the diagnosis and treatment of cerebrovascular diseases, brain tumors and traumatic brain injuries. Song is also one of the main researchers in China whose research interests include the clinical and fundamental studies of cerebrovascular diseases and brain injuries, especially in subarachnoid hemorrhage and diffuse axonal injury.

Ming Zhang

Ming Zhang, whose medical training culminated with a doctorate in Neurosurgery in Xi’an Jiaotong University, worked on store-operated calcium channels and mammalian TRP channels after stroke with Jin-Ning Song, and currently focuses on functional properties and regulation of ion transport mechanisms in subarachnoid hemorrhage and cerebral ischemia.

Acknowledgment

All of the authors involved in the preparation of the above manuscript declare no conflict of interest in any form.

References

Abbott, N.J., Rönnbäck, L., and Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41–53.10.1038/nrn1824Search in Google Scholar

Abbott, N.J., Patabendige, A.A.K., Dolman, D.E.M., Yusof, S.R., and Begley, D.J. (2010). Structure and function of the blood-brain barrier. Neurobiol. Dis. 37, 13–25.10.1016/j.nbd.2009.07.030Search in Google Scholar

Andjelkovic, A.V., Song, L., Dzenko, K.A., Cong, H., and Pachter, J.S. (2002). Functional expression of CCR2 by human fetal astrocytes. J. Neurosci. Res. 70, 219–231.10.1002/jnr.10372Search in Google Scholar

András, I.E., Eum, S.Y., and Toborek, M. (2012). Lipid rafts and functional caveolae regulate HIV-induced amyloid β accumulation in brain endothelial cells. Biochem. Biophys. Res. Commun. 2, 177–183.10.1016/j.bbrc.2012.03.128Search in Google Scholar

Barakat, S., Demeule, M., Pilorget, A., Régina, A., Gingras, D., Baggetto, L.G., and Béliveau, R. (2007). Modulation of p-glycoprotein function by caveolin-1 phosphorylation. J. Neurochemistry 101, 1–8.10.1111/j.1471-4159.2006.04410.xSearch in Google Scholar

Bauer, P.M., Yu, J., Chen, Y., Hickey, R., Bernatchez, P.N., Looft-Wilson, R., Huang, Y., Giordano, F., Stan, R.V., and Sessa, W.C. (2005). Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Sci. Signal. 102, 204.10.1073/pnas.0406092102Search in Google Scholar

Beauchesne, É., Desjardins, P., Butterworth, R.F., and Hazell, A.S. (2010). Up-regulation of caveolin-1 and blood-brain barrier breakdown are attenuated by N-acetylcysteine in thiamine deficiency. Neurochem. Int. 57, 830–837.10.1016/j.neuint.2010.08.022Search in Google Scholar

Chansel, D., Ciroldi, M., Vandermeersch, S., Jackson, L.F., Gomez, A.M., Henrion, D., Lee, D.C., Coffman, T.M., Richard, S., and Dussaule, J.C. (2006). Heparin binding EGF is necessary for vasospastic response to endothelin. FASEB J. 20, 1936–1938.10.1096/fj.05-5328fjeSearch in Google Scholar

Dejana, E., Spagnuolo, R., and Bazzoni, G. (2001). Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration. Thromb. Haemostasis 86, 308–315.10.1055/s-0037-1616228Search in Google Scholar

Demeule, M., Jodoin, J., Gingras, D., and Béliveau, R. (2000). P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Lett. 466, 219–224.10.1016/S0014-5793(00)01087-5Search in Google Scholar

Deng, J., Huang, Q., Wang, F., Liu, Y., Wang, Z., Zhang, Q., Lei, B., and Cheng, Y. (2012). The role of caveolin-1 in blood-brain barrier disruption induced by focused ultrasound combined with microbubbles. J. Mol. Neurosci. 46, 677–687.10.1007/s12031-011-9629-9Search in Google Scholar PubMed

Doherty, G.J. and McMahon, H.T. (2009). Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902.10.1146/annurev.biochem.78.081307.110540Search in Google Scholar PubMed

Dzenko, K.A., Andjelkovic, A.V., Kuziel, W.A., and Pachter, J.S. (2001). The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels. J. Neurosci. 21, 9214–9223.10.1523/JNEUROSCI.21-23-09214.2001Search in Google Scholar

Frank, P.G., Pavlides, S., and Lisanti, M.P. (2009). Caveolae and transcytosis in endothelial cells: role in atherosclerosis. Cell Tissue Res. 335, 41–47.10.1007/s00441-008-0659-8Search in Google Scholar PubMed

Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., and Tsukita, S. (1993). Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 123, 1777–1788.10.1083/jcb.123.6.1777Search in Google Scholar PubMed PubMed Central

García-Cardeña, G., Fan R., Stern D.F., Liu J., and Sessa W.C. (1996a). Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1. J. Biol. Chem. 271, 27237–27240.10.1074/jbc.271.44.27237Search in Google Scholar PubMed

García-Cardeña, G., Oh, P., Liu, J., Schnitzer, J.E., and Sessa, W.C. (1996b). Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc. Natl. Acad. Sci. USA 93, 6448–6453.10.1073/pnas.93.13.6448Search in Google Scholar PubMed PubMed Central

Ge, S. and Pachter, J.S. (2004). Caveolin-1 knockdown by small interfering RNA suppresses responses to the chemokine monocyte chemoattractant protein-1 by human astrocytes. J. Biol Chem. 279, 6688–6695.10.1074/jbc.M311769200Search in Google Scholar PubMed

Ge, S., Song, L., Serwanski, D.R., Kuziel, W.A., and Pachter, J.S. (2007). Transcellular transport of CCL2 across brain microvascular endothelial cells. J. Neurochem. 104, 1219–1232.10.1111/j.1471-4159.2007.05056.xSearch in Google Scholar PubMed

Gottschall, P.E. and Barone, F.C. (2012). Important role for endothelial calveolin-1 in focal cerebral ischemia-induced blood-brain barrier injury. J. Neurochem. 120, 4–6.10.1111/j.1471-4159.2011.07546.xSearch in Google Scholar PubMed PubMed Central

Gratton, J.P., Lin, M.I., Yu, J., Weiss, E.D., Jiang, Z.L., Fairchild, T.A., Iwakiri, Y., Groszmann, R., Claffey, K.P., and Cheng, Y.C. (2003). Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 4, 31–39.10.1016/S1535-6108(03)00168-5Search in Google Scholar

Gu, Z., Kaul, M., Yan, B., Kridel, S.J., Cui, J., Strongin, A., Smith, J.W., Liddington, R.C., and Lipton, S.A. (2002). S-Nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Sci. Signal. 297, 1186.10.1126/science.1073634Search in Google Scholar PubMed

Gu, Y., Dee, C., and Shen, J. (2011a). Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability. Front. Biosci. 3, 1216–1231.10.2741/s222Search in Google Scholar

Gu, Y., Xue, Y., Zhang, H., Li, Y., and Liang, X. (2011b). Adenosine 5′-triphosphate-sensitive potassium channel activator induces the up-regulation of caveolin-1 expression in a rat brain tumor model. Cell. Mol. Neurobiol. 31, 629–634.10.1007/s10571-011-9658-5Search in Google Scholar PubMed

Gu, Y., Zheng, G., Xu, M., Li, Y., Chen, X., Zhu, W., Tong, Y., Chung, S.K., Liu, K.J., and Shen, J. (2012). Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury. J. Neurochem. 1, 147–156.10.1111/j.1471-4159.2011.07542.xSearch in Google Scholar PubMed

Gumbleton, M., Abulrob, A.G., and Campbell, L. (2000). Caveolae: an alternative membrane transport compartment. Pharm. Res. 17, 1035–1048.10.1023/A:1026464526074Search in Google Scholar

Hawkins, B.T. and Davis, T.P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev. 57, 173–185.10.1124/pr.57.2.4Search in Google Scholar PubMed

Hawkins, B.T., Sykes, D.B., and Miller, D.S. (2010). Rapid, reversible modulation of blood-brain barrier P-glycoprotein transport activity by vascular endothelial growth factor. J. Neurosci. 30, 1417–1425.10.1523/JNEUROSCI.5103-09.2010Search in Google Scholar PubMed PubMed Central

Hayashi, Y.K., Matsuda, C., Ogawa, M., Goto, K., Tominaga, K., Mitsuhashi, S., Park, Y.-E., Nonaka, I., Hino-Fukuyo, N., and Haginoya, K. (2009). Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J. Clin. Invest. 119, 2623.10.1172/JCI38660Search in Google Scholar PubMed PubMed Central

Huang, W., András, I.E., Rha, G.B., Hennig, B., and Toborek, M. (2011). PPARα and PPARγ protect against HIV-1-induced MMP-9 overexpression via caveolae-associated ERK and Akt signaling. FASEB J. 25, 3979–3988.10.1096/fj.11-188607Search in Google Scholar PubMed PubMed Central

Iwamoto, R. and Mekada, E. (2000). Heparin-binding EGF-like growth factor: a juxtacrine growth factor. Cytokine Growth Factor Rev. 11, 335–344.10.1016/S1359-6101(00)00013-7Search in Google Scholar

Jasmin, J.F., Malhotra, S., Dhallu, M.S., Mercier, I., Rosenbaum, D.M., and Lisanti, M.P. (2007). Caveolin-1 deficiency increases cerebral ischemic injury. Circ. Res. 100, 721–729.10.1161/01.RES.0000260180.42709.29Search in Google Scholar

Jetté, L., Têtu, B., and Béliveau, R. (1993). High levels of P-glycoprotein detected in isolated brain capillaries. Biochim. Biophys. Acta Biomembr. 1150, 147–154.10.1016/0005-2736(93)90083-CSearch in Google Scholar

Jodoin, J., Demeule, M., Fenart, L., Cecchelli, R., Farmer, S., Linton, K.J., Higgins, C.F., and Béliveau, R. (2004). P-glycoprotein in blood-brain barrier endothelial cells: interaction and oligomerization with caveolins. J. Neurochem. 87, 1010–1023.10.1046/j.1471-4159.2003.02081.xSearch in Google Scholar PubMed

Kim, M., Park, S., Kopetz, S., and Gallick, G. (2009). Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. Cell Tissue Res. 335, 249–259.10.1007/s00441-008-0682-9Search in Google Scholar PubMed PubMed Central

Lakhan, S.E., Kirchgessner, A., Tepper, D., and Leonard, A. (2013). Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke. Front. Neurol. 4, 32.10.3389/fneur.2013.00032Search in Google Scholar PubMed PubMed Central

Liu, J., Razani, B., Tang, S., Terman, B.I., Ware, J.A., and Lisanti, M.P. (1999). Angiogenesis activators and inhibitors differentially regulate caveolin-1 expression and caveolae formation in vascular endothelial cells angiogenesis inhibitors block vascular endothelial growth factor-induced down-regulation of caveolin-1. J. Biol. Chem. 274, 15781–15785.10.1074/jbc.274.22.15781Search in Google Scholar PubMed

Liu, L., Xue, Y., and Liu, Y. (2010). Bradykinin increases the permeability of the blood-tumor barrier by the caveolae-mediated transcellular pathway. J. Neuro-oncol. 99, 187–194.10.1007/s11060-010-0124-xSearch in Google Scholar PubMed

Liu, J., Jin, X., Liu, K.J., and Liu, W. (2012). Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage. J. Neurosci. 32, 3044–3057.10.1523/JNEUROSCI.6409-11.2012Search in Google Scholar PubMed PubMed Central

Long, M., Huang, S.H., Wu, C.H., Shackleford, G.M., and Jong, A. (2012). Lipid raft/caveolae signaling is required for Cryptococcus neoformans invasion into human brain microvascular endothelial cells. J. Biomed. Sci. 19, 19.10.1186/1423-0127-19-19Search in Google Scholar PubMed PubMed Central

Luker, G.D., Pica, C.M., Kumar, A.S., Covey, D.F., and Piwnica-Worms, D. (2000). Effects of cholesterol and enantiomeric cholesterol on P-glycoprotein localization and function in low-density membrane domains. Biochemistry 39, 7651–7661.10.1021/bi9928593Search in Google Scholar PubMed

McCaffrey, G., Staatz, W.D., Sanchez-Covarrubias, L., Finch, J.D., DeMarco, K., Laracuente, M.L., Ronaldson, P.T., and Davis, T.P. (2012). P-glycoprotein trafficking at the blood-brain barrier altered by peripheral inflammatory hyperalgesia. J. Neurochem. 5, 962–975.10.1111/j.1471-4159.2012.07831.xSearch in Google Scholar PubMed PubMed Central

Nag, S., Venugopalan, R., and Stewart, D.J. (2007). Increased caveolin-1 expression precedes decreased expression of occludin and claudin-5 during blood-brain barrier breakdown. Acta Neuropathol. 114, 459–469.10.1007/s00401-007-0274-xSearch in Google Scholar PubMed

Nag, S., Manias, J., and Stewart, D. (2009). Expression of endothelial phosphorylated caveolin-1 is increased in brain injury. Neuropathol. Appl. Neurobiol. 35, 417–426.10.1111/j.1365-2990.2008.01009.xSearch in Google Scholar PubMed

Nusrat, A., Parkos, C., Verkade, P., Foley, C., Liang, T., Innis-Whitehouse, W., Eastburn, K., and Madara, J. (2000). Tight junctions are membrane microdomains. J. Cell Sci. 113, 1771–1781.10.1242/jcs.113.10.1771Search in Google Scholar PubMed

Palmela, I., Cardoso, F.L., Bernas, M., Correia, L., Vaz, A.R., Silva, R., Fernandes, A., Kim, K.S., Brites, D., and Brito, M.A. (2011). Elevated levels of bilirubin and long-term exposure impair human brain microvascular endothelial cell integrity. Curr. Neurovasc. Res. 8, 153–169.10.2174/156720211795495358Search in Google Scholar PubMed

Palmela, I., Sasaki, H., Cardoso, F.L., Moutinho, M., Kim, K.S., Brites, D., and Brito, M.A. (2012). Time-dependent dual effects of high levels of unconjugated bilirubin on the human blood-brain barrier lining. Front. Cell. Neurosci. 6, 22.10.3389/fncel.2012.00022Search in Google Scholar PubMed PubMed Central

Pedram, A., Razandi, M., and Levin, E.R. (2002). Deciphering vascular endothelial cell growth factor/vascular permeability factor signaling to vascular permeability inhibition by atrial natriuretic peptide. J. Biol. Chem. 277, 44385–44398.10.1074/jbc.M202391200Search in Google Scholar PubMed

Persidsky, Y., Heilman, D., Haorah, J., Zelivyanskaya, M., Persidsky, R., Weber, G.A., Shimokawa, H., Kaibuchi, K., and Ikezu, T. (2006). Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood 107, 4770–4780.10.1182/blood-2005-11-4721Search in Google Scholar PubMed PubMed Central

Razani, B., Engelman, J.A., Wang, X.B., Schubert, W., Zhang, X.L., Marks, C.B., Macaluso, F., Russell, R.G., Li, M., and Pestell, R.G. (2001). Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J. Biol. Chem. 276, 38121–38138.10.1074/jbc.M105408200Search in Google Scholar PubMed

Rothnie, A., Theron, D., Soceneantu, L., Martin, C., Traikia, M., Berridge, G., Higgins, C.F., Devaux, P.F., and Callaghan, R. (2001). The importance of cholesterol in maintenance of P-glycoprotein activity and its membrane perturbing influence. Eur. Biophys. J. 30, 430–442.10.1007/s002490100156Search in Google Scholar

Salcedo, R., Ponce, M.L., Young, H.A., Wasserman, K., Ward, J.M., Kleinman, H.K., Oppenheim, J.J., and Murphy, W.J. (2000). Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 96, 34–40.10.1182/blood.V96.1.34Search in Google Scholar

Schinkel, A.H. (1999). P-glycoprotein, a gatekeeper in the blood-brain barrier. Adv. Drug Delivery Rev. 36, 179–194.10.1016/S0169-409X(98)00085-4Search in Google Scholar

Schlachetzki, F. and Pardridge, W.M. (2003). P-glycoprotein and caveolin-1 [alpha] in endothelium and astrocytes of primate brain. Neuroreport 14, 2041–2046.10.1097/00001756-200311140-00007Search in Google Scholar PubMed

Schubert, W., Frank, P.G., Woodman, S.E., Hyogo, H., Cohen, D.E., Chow, C.W., and Lisanti, M.P. (2002). Microvascular hyperpermeability in caveolin-1-/- knock-out mice treatment with a specific nitric-oxide synthase inhibitor, l-NAME, restores normal microvascular permeability in Cav-1 null mice. J. Biol. Chem. 277, 40091–40098.10.1074/jbc.M205948200Search in Google Scholar PubMed

Shen, J., Ma, S., Chan, P., Lee, W., Fung, P.C.W., Cheung, R.T.F., Tong, Y., and Liu, K.J. (2006). Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury. J. Neurochem. 96, 1078–1089.10.1111/j.1471-4159.2005.03589.xSearch in Google Scholar PubMed

Smith, M.W. and Gumbleton, M. (2006). Endocytosis at the blood-brain barrier: from basic understanding to drug delivery strategies. J. Drug Targeting 14, 191–214.10.1080/10611860600650086Search in Google Scholar PubMed

Song, L. and Pachter, J.S. (2004). Monocyte chemoattractant protein-1 alters expression of tight junction-associated proteins in brain microvascular endothelial cells. Microvasc. Res. 67, 78.10.1016/j.mvr.2003.07.001Search in Google Scholar PubMed

Song, L., Ge, S., and Pachter, J.S. (2007). Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells. Blood 109, 1515–1523.10.1182/blood-2006-07-034009Search in Google Scholar PubMed PubMed Central

Stone, K.P., Kastin, A.J., and Pan, W. (2011). NF-ĸB is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia. Cell. Physiol. Biochem. 28, 115–124.10.1159/000331720Search in Google Scholar PubMed PubMed Central

van den Heuvel, A.P., Schulze, A., and Burgering, B.M. (2005). Direct control of caveolin-1 expression by FOXO transcription factors. Biochem J. 385, 795–802.10.1042/BJ20041449Search in Google Scholar

Virgintino, D., Robertson, D., Errede, M., Benagiano, V., Girolamo, F., Maiorano, E., Roncali, L., and Bertossi, M. (2002a). Expression of P-glycoprotein in human cerebral cortex microvessels. J. Histochem. Cytochem. 50, 1671–1676.10.1177/002215540205001212Search in Google Scholar

Virgintino, D., Robertson, D., Errede, M., Benagiano, V., Tauer, U., Roncali, L., and Bertossi, M. (2002b). Expression of caveolin-1 in human brain microvessels. Neuroscience 115, 145–152.10.1016/S0306-4522(02)00374-3Search in Google Scholar

Wang, W., Dentler, W.L., and Borchardt, R.T. (2001). VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am. J. Physiol. Heart Circ. Physiol. 280, H434–H440.10.1152/ajpheart.2001.280.1.H434Search in Google Scholar PubMed

Wang, P., Xue, Y., Shang, X., and Liu, Y. (2010). Diphtheria toxin mutant CRM197-mediated transcytosis across blood-brain barrier in vitro. Cell. Mol. Neurobiol. 30, 717–725.10.1007/s10571-010-9496-xSearch in Google Scholar PubMed

Wang, P., Liu, Y., Shang, X., and Xue, Y. (2011). CRM197-induced blood-brain barrier permeability increase is mediated by upregulation of caveolin-1 protein. J. Mol. Neurosci. 43, 485–492.10.1007/s12031-010-9471-5Search in Google Scholar PubMed

Wu, D. and Terrian, D.M. (2002). Regulation of caveolin-1 expression and secretion by a protein kinase cepsilon signaling pathway in human prostate cancer cells. J Biol Chem. 277, 40449–40455.10.1074/jbc.M206270200Search in Google Scholar PubMed

Xia, C., Zhang, Z., Xue, Y., Wang, P., and Liu, Y. (2009). Mechanisms of the increase in the permeability of the blood-tumor barrier obtained by combining low-frequency ultrasound irradiation with small-dose bradykinin. J. Neuro-oncol. 94, 41–50.10.1007/s11060-009-9812-9Search in Google Scholar PubMed

Xia, C., Liu, Y., Wang, P., and Xue, Y. (2012). Low-frequency ultrasound irradiation increases blood-tumor barrier permeability by transcellular pathway in a rat glioma model. J. Mol. Neurosci. 48, 1–10.10.1007/s12031-012-9770-0Search in Google Scholar PubMed

Xie, Z., Zeng, X., Waldman, T., and Glazer, R.I. (2003). Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 activates β-catenin and c-Myc, and down-regulates caveolin-1. Cancer Res. 63, 5370–5375.Search in Google Scholar

Xu, R., Feng, X., Xie, X., Zhang, J., Wu, D., and Xu, L. (2011). HIV-1 Tat protein increases the permeability of brain endothelial cells by both inhibiting occludin expression and cleaving occludin via matrix metalloproteinase-9. Brain Res. 1436, 13–19.10.1016/j.brainres.2011.11.052Search in Google Scholar PubMed

Yang, Y., Estrada, E.Y., Thompson, J.F., Liu, W., and Rosenberg, G.A. (2006). 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, 697–709.10.1038/sj.jcbfm.9600375Search in Google Scholar PubMed

Zhao, L., Yang, Z., Liu, Y., Ying, H., Zhang, H., and Xue, Y. (2011). Vascular endothelial growth factor increases permeability of the blood-tumor barrier via caveolae-mediated transcellular pathway. J. Mol. Neurosci. 44, 122–129.10.1007/s12031-010-9487-xSearch in Google Scholar PubMed

Zhong, Y., Smart, E.J., Weksler, B., Couraud, P.O., Hennig, B., and Toborek, M. (2008). Caveolin-1 regulates HIV-1 Tat-induced alterations of tight junction protein expression via modulation of the Ras signaling. J. Neurosci. 28, 7788–7796.10.1523/JNEUROSCI.0061-08.2008Search in Google Scholar PubMed PubMed Central

Zhong, Y., Hennig, B., and Toborek, M. (2009). Intact lipid rafts regulate HIV-1 Tat protein-induced activation of the Rho signaling and upregulation of P-glycoprotein in brain endothelial cells. J. Cereb. Blood Flow Metab. 30, 522–533.10.1038/jcbfm.2009.214Search in Google Scholar PubMed PubMed Central

Zhou, J., Li, J., Rosenbaum, D.M., and Barone, F.C. (2010). Thrombopoietin protects the brain and improves sensorimotor functions: reduction of stroke-induced MMP-9 upregulation and blood-brain barrier injury. J. Cereb. Blood Flow Metab. 31, 924–933.10.1038/jcbfm.2010.171Search in Google Scholar PubMed PubMed Central

Received: 2013-9-2
Accepted: 2013-12-26
Published Online: 2014-2-6
Published in Print: 2014-4-1

©2014 by Walter de Gruyter Berlin/Boston

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