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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2787-2794. Prepublished online as a Blood First Edition Paper on July 15, 2008; DOI 10.1182/blood-2008-02-141630. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-141630v1 112/7/2787    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by An, J. Articles by Yepes, M. Search for Related Content PubMed PubMed Citation Articles by An, J. Articles by Yepes, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Tissue-type plasminogen activator and the low-density lipoprotein receptor–related protein induce Akt phosphorylation in the ischemic brain Jie An1,2,*, Chen Zhang2, Rohini Polavarapu2, Xiaohui Zhang2, Xiumei Zhang1, and Manuel Yepes2 1 Institute of Pharmacology, Shandong University School of Medicine, Jinan, China; and 2 Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA Tissue-type plasminogen activator (tPA) is found in the intravascular space and in the central nervous system. The low-density lipoprotein receptor–related protein (LRP) is expressed in neurons and in perivascular astrocytes. During cerebral ischemia, tPA induces the shedding of LRP's extracellular domain from perivascular astrocytes, and this is followed by the development of cerebral edema. Protein kinase B (Akt) is a serine/threonine kinase that plays a critical role not only in cell survival but also in the regulation of the permeability of the blood-brain barrier. We found that, in the early phases of the ischemic insult, the interaction between tPA and LRP induces Akt phosphorylation (pAkt) in perivascular astrocytes and inhibits pAkt in neurons. Coimmunoprecipitation studies indicate that pAkt and LRP's intracellular domain interact in perivascular astrocytes and that this interaction is dependent on the presence of tPA and results in the development of edema. Together, these results indicate that, in the early stages of cerebral ischemia, the interaction between tPA and LRP in perivascular astrocytes induces the activation of a cell signaling event mediated by pAkt that leads to increase in the permeability of the blood-brain barrier. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. D. Roussel, R. Macrez, A. Jullienne, V. Agin, E. Maubert, L. Dauphinot, M.-C. Potier, L. Plawinski, H. Castel, Y. Hommet, et al. Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact Brain, July 2, 2009; (2009) awp162v1. [Abstract] [Full Text] [PDF] A. Gaultier, X. Wu, N. Le Moan, S. Takimoto, G. Mukandala, K. Akassoglou, W. M. Campana, and S. L. Gonias Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis J. Cell Sci., April 15, 2009; 122(8): 1155 - 1162. [Abstract] [Full Text] [PDF] C. Zhang, J. An, D. K. Strickland, and M. Yepes The Low-Density Lipoprotein Receptor-Related Protein 1 Mediates Tissue-Type Plasminogen Activator-Induced Microglial Activation in the Ischemic Brain Am. J. Pathol., February 1, 2009; 174(2): 586 - 594. [Abstract] [Full Text] [PDF]

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