Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Extracellular Alterations in Ph and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome

Version 1 : Received: 3 June 2022 / Approved: 6 June 2022 / Online: 6 June 2022 (05:51:59 CEST)

A peer-reviewed article of this Preprint also exists.

Wahl, 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. Extracellular Alterations in pH and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome. Pharmaceutics 2022, 14, 1469. Wahl, 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. Extracellular Alterations in pH and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome. Pharmaceutics 2022, 14, 1469.

Journal reference: Pharmaceutics 2022, 14, 1469
DOI: 10.3390/pharmaceutics14071469

Abstract

Pathologies of the blood brain barrier (BBB) have been linked to a multitude of 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 full understanding remains elusive. This study utilized an in vitro model of the BBB with b.End3 murine endothelial cells to investigate the role of CSD in BBB pathology by characterizing effects of the release of major pronociceptive substances on BBB functional integrity using TEER screening, transcellular uptake, and immunoreactive methods in concert with global proteome and phospho-proteomic approaches. Findings demonstrated relocalization and functional alteration to proteins associated with the cytoskeleton and endothelial tight junctions. Pathologic mechanisms induced by individual substances released during CSD were found to have unique phosphorylation signatures in phospho-proteome analysis, identifying Zona Occludens 1 as a possible pathologic “checkpoint” of the BBB. Utilizing these phosphorylation signatures, possible novel diagnostic methods may be developed for neurological diseases and warrants further investigation.

Keywords

Blood Brain Barrier; pH; Proteome; Phospho-Proteome; Endothelial

Subject

MEDICINE & PHARMACOLOGY, Other

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