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

Wahl, Jared; Vivek, Anjali; Palomino, Seph M.; Almuslim, Moyad; Cottier, Karissa E.; Langlais, Paul; Streicher, John M.; Vanderah, Todd W.; Liktor‐Busa, Erika; Largent-Milnes, Tally M.

doi:10.3390/pharmaceutics14071469

Cited by 3 publications

(6 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This same group also showed that HSP90 inhibition prevented a reduction in TJ proteins occludin and ZO-1 [36]. Previously, we reported that CSD induction with cortical injection of KCl does not significantly change detection of TJ proteins (i.e., claudin 5) in cortex or brainstem as compared to aCSF controls [11]; however, KCl pulse decreases corrected total cell fluorescence of claudin 5 as compared to controls in bEnD.3 cells, but no significant changes in the surface levels of claudin 5 were observed after KCl treatment [23].…”

Section: Discussionmentioning

confidence: 83%

“…We have previously observed that high extracellular K + promotes ZO-1 phosphorylation in bEnd.3 endothelial cells. Thus, 17-AAG may be preventing ZO-1 degradation to indirectly increase detection of claudin 5 [23].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we asked whether inhibition of HSP90 with 17-AAG changed expression of the tight junction protein claudin 5. Our previous studies using in vivo or in vitro techniques have indicated that cortical injection of KCl or KCl pulse in vitro does not change claudin 5 expression in cortical capillaries or endothelial cells as compared to naive or aCSF injected controls, respectively [11,23]. Therefore, cortical tissues from vehicle pretreated and 17AAG pretreated cortical tissues were compared.…”

Section: -Aag Increases Detection Of Claudin 5 Total Protein After Co...mentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of HSP90 Preserves Blood–Brain Barrier Integrity after Cortical Spreading Depression

et al. 2022

Self Cite

View full text Add to dashboard Cite

Cortical spreading depression (CSD) is a pathophysiological mechanism underlying headache disorders, including migraine. Blood–brain barrier (BBB) permeability is increased during CSD. Recent papers have suggested that heat shock proteins (HSP) contribute to the integrity of the blood–brain barrier. In this study, the possible role of HSP90 in CSD-associated blood–brain barrier leak at the endothelial cell was investigated using an in vitro model, for the blood–endothelial barrier (BEB), and an in vivo model with an intact BBB. We measured barrier integrity using trans endothelial electric resistance (TEER) across a monolayer of rodent brain endothelial cells (bEnd.3), a sucrose uptake assay, and in situ brain perfusion using female Sprague Dawley rats. CSD was induced by application of 60 mM KCl for 5 min in in vitro experiments or cortical injection of KCl (1 M, 0.5 µL) through a dural cannula in vivo. HSP90 was selectively blocked by 17-AAG. Our data showed that preincubation with 17-AAG (1 µM) prevented the reduction of TEER values caused by the KCl pulse on the monolayer of bEnd.3 cells. The elevated uptake of 14C-sucrose across the same endothelial monolayer induced by the KCl pulse was significantly reduced after preincubation with HSP90 inhibitor. Pre-exposure to 17-AAG significantly mitigated the transient BBB leak after CSD induced by cortical KCl injection as determined by in situ brain perfusion in female rats. Our results demonstrated that inhibition of HSP90 with the selective agent 17-AAG reduced CSD-associated BEB/BBB paracellular leak. Overall, this novel observation supports HSP90 inhibition mitigates KCl-induced BBB permeability and suggests the development of new therapeutic approaches targeting HSP90 in headache disorders.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: -Aag Increases Detection Of Claudin 5 Total Protein After Co...mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of HSP90 Preserves Blood–Brain Barrier Integrity after Cortical Spreading Depression

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Low gravity simulation and spaceflight have been shown to negatively impact the blood-brain barrier. Proteomics showed alterations in the expression of cell-cell adhesion molecules and Zonula occludins-1, a key component of tight junctions [226].…”

Section: Cell-cell Adhesions and Tight Junctions In Low Gravitymentioning

confidence: 99%

Receptors Implicated in Microgravity-Induced Bone Loss

Martinez,

Pelegrine,

Holliday

2024

Receptors

View full text Add to dashboard Cite

For humans to explore and colonize the universe, both engineering and physiological obstacles must be successfully addressed. A major physiological problem is that humans lose bone rapidly in microgravity. Understanding the underlying mechanisms for this bone loss is crucial for designing strategies to ameliorate these effects. Because bone physiology is entangled with other organ systems, and bone loss is a component of human adaptation to microgravity, strategies to reduce bone loss must also account for potential effects on other systems. Here, we consider the receptors involved in normal bone remodeling and how this regulation is altered in low-gravity environments. We examine how single cells, tissues and organs, and humans as a whole are affected by low gravity, and the role of receptors that have been implicated in responses leading to bone loss. These include receptors linking cells to the extracellular matrix and to each other, alterations in the extracellular matrix associated with changes in gravity, and changes in fluid distribution and fluid behavior due to lack of gravity that may have effects on receptor-based signaling shared by bone and other regulatory systems. Inflammatory responses associated with the environment in space, which include microgravity and radiation, can also potentially trigger bone loss.

show abstract

“…Progenesis QI for proteomics software (version 2.4, Nonlinear Dynamics Ltd., Newcastle upon Tyne, UK) was used to perform ion-intensity based label-free quantification as previously described [63][64][65][66]. In brief, in an automated format, .raw files were imported and converted into two-dimensional maps (y-axis = time, x-axis = m/z) followed by the selection of a reference run for alignment purposes.…”

Section: Label-free Quantitative Proteomicsmentioning

confidence: 99%

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells

Iannuzo

Guerra

et al. 2023

Cells

Self Cite

View full text Add to dashboard Cite

Club Cell Secretory Protein (CC16) plays many protective roles within the lung; however, the complete biological functions, especially regarding the pulmonary epithelium during infection, remain undefined. We have previously shown that CC16-deficient (CC16−/−) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden compared to CC16-sufficient (WT) MTECs; therefore, in this study, we wanted to further define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air–liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When challenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16−/− MTECs have increased apical protein secretion compared to their unchallenged controls. Following Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16−/− MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings suggest that CC16 may be important in providing protection within the pulmonary epithelium during respiratory infection with Mp, which is the major causative agent of community-acquired pneumoniae.

show abstract

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

Cited by 3 publications

References 50 publications

Inhibition of HSP90 Preserves Blood–Brain Barrier Integrity after Cortical Spreading Depression

Inhibition of HSP90 Preserves Blood–Brain Barrier Integrity after Cortical Spreading Depression

Receptors Implicated in Microgravity-Induced Bone Loss

The Impact of CC16 on Pulmonary Epithelial-Driven Host Responses during Mycoplasma pneumoniae Infection in Mouse Tracheal Epithelial Cells

Contact Info

Product

Resources

About