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dc.contributor.authorWahl, J.R.
dc.contributor.authorVivek, A.
dc.contributor.authorPalomino, S.M.
dc.contributor.authorAlmuslim, M.
dc.contributor.authorCottier, K.E.
dc.contributor.authorLanglais, P.R.
dc.contributor.authorStreicher, J.M.
dc.contributor.authorVanderah, T.W.
dc.contributor.authorLiktor-Busa, E.
dc.contributor.authorLargent-Milnes, T.M.
dc.date.accessioned2022-10-24T23:51:16Z
dc.date.available2022-10-24T23:51:16Z
dc.date.issued2022
dc.identifier.citationWahl, J. R., Vivek, A., Palomino, S. M., Almuslim, M., Cottier, K. E., Langlais, P. R., Streicher, J. M., Vanderah, T. W., Liktor-Busa, E., & Largent-Milnes, T. M. (2022). Extracellular Alterations in pH and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome. Pharmaceutics, 14(7).
dc.identifier.issn1999-4923
dc.identifier.doi10.3390/pharmaceutics14071469
dc.identifier.urihttp://hdl.handle.net/10150/666476
dc.description.abstractPathologies of the blood–brain barrier (BBB) have been linked to a multitude of central nervous system (CNS) disorders whose pathology is poorly understood. Cortical spreading depression (CSD) has long been postulated to be involved in the underlying mechanisms of these disease states, yet a complete understanding remains elusive. This study seeks to utilize an in vitro model of the blood–brain barrier (BBB) with brain endothelial cell (b.End3) murine endothelioma cells to investigate the role of CSD in BBB pathology by characterizing effects of the release of major pronociceptive substances into the extracellular space of the CNS. The application of trans-endothelial electrical resistance (TEER) screening, transcellular uptake, and immunoreactive methods were used in concert with global proteome and phospho-proteomic approaches to assess the effect of modeled CSD events on the modeled BBB in vitro. The findings demonstrate relocalization and functional alteration to proteins associated with the actin cytoskeleton and endothelial tight junctions. Additionally, unique pathologic mechanisms induced by individual substances released during CSD were found to have unique phosphorylation signatures in phospho-proteome analysis, identifying Zona Occludins 1 (ZO-1) as a possible pathologic “checkpoint” of the BBB. By utilizing these phosphorylation signatures, possible novel diagnostic methods may be developed for CSD and warrants further investigation. © 2022 by the authors.
dc.language.isoen
dc.publisherMDPI
dc.rightsCopyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectblood–brain barrier
dc.subjectendothelial
dc.subjectpH
dc.subjectphospho-proteome
dc.subjectproteome
dc.titleExtracellular Alterations in pH and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome
dc.typeArticle
dc.typetext
dc.contributor.departmentDepartment of Pharmacology, University of Arizona
dc.identifier.journalPharmaceutics
dc.description.noteOpen access journal
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
dc.eprint.versionFinal published version
dc.source.journaltitlePharmaceutics
refterms.dateFOA2022-10-24T23:51:16Z


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Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).