Expression of caveolin-1 in human brain microvessels

Virgintino, Daniela; Robertson, David; Errede, Mariella; Benagiano, Vincenzo; Tauer, Ulrike; Roncali, Luisa; Bertossi, M

doi:10.1016/s0306-4522(02)00374-3

Cited by 96 publications

(78 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caveolae is microdomain localized within the cellular membranes which contain the caveolin family of proteins named caveolins-1, -2 and -3. In the brain, caveolin-1 has been shown to be highly expressed in brain microvessels and more specifically in endothelial cells (Ikezu et al 1998;Virgintino et al 2002). Caveolin-1 is the main constituent of caveolae; caveolin-1 expression is critical for the regulation of BBB permeability.…”

Section: Discussionmentioning

confidence: 99%

Diphtheria Toxin Mutant CRM197-Mediated Transcytosis across Blood–Brain Barrier In Vitro

et al. 2010

View full text Add to dashboard Cite

Blood-brain barrier (BBB) is specialized to limit brain drug delivery. Cross-reacting material 197 (CRM197), a non-toxic mutant of diphtheria toxin, could act as a diphtheria toxin receptor-specific carrier protein and deliver drugs across the BBB. CRM197 has previously been shown to inhibit phospatidyl-3-inositol-kinase (PI3K)/Akt signaling. Other studies have demonstrated a link between PI3K/Akt signaling and forkhead transcription factors in endothelial cells. We therefore investigated the effects and mechanisms underlying the potential of CRM197, not only as a carrier protein for targeted drug delivery to the brain, but also for inducing signaling to affect endocytosis in endothelial cells. The hCMEC/D3 cell line had been used to establish a BBB in vitro model; the transport efficiency of CRM197 was analyzed both by association and transcytosis experiments. CRM197 was shown to prefer apical-to-basal transcytosis, which involved the caveolae-mediated pathway. The uptake of CRM197 conjugates by endothelial cells reached equilibrium after 60 min of treatment. The caveolin-1 mRNA and protein expression levels were significantly increased by CRM197. The up-regulation of caveolin-1 may be mediated by CRM197 via a PI3K/Akt dependent pathway and reduction of the phospho-FOXO1A (forkhead box O) transcription factor. Our results indicate that carrier protein CRM197-mediated delivery across the BBB is involved in the induction of FOXO1A transcriptional activity and upregulation of caveolin-1 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Diphtheria Toxin Mutant CRM197-Mediated Transcytosis across Blood–Brain Barrier In Vitro

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Endothelial cells are known to express the highest levels of caveolin-1. 76 Virgintino et al 77 have reported that caveolin-1 and -2 are found in rat microvessels, and caveolin-1 is expressed in the human BBB. In the primate BBB, confocal microscopic studies indicate caveolin-1 is found in both endothelium and astrocytes.…”

Section: Caveolin-1 In Bbb Endotheliamentioning

confidence: 99%

Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

2005

View full text Add to dashboard Cite

Summary:Immunogold electron microscopy has identified a variety of blood-brain barrier (BBB) proteins with transporter and regulatory functions. For example, isoforms of the glucose transporter, protein kinase C (PKC), and caveolin-1 are BBB specific. Isoform 1 of the facilitative glucose transporter family (GLUT1) is expressed solely in endothelial (and pericyte) domains, and ϳ75% of the protein is membrane-localized in humans. Evidence is presented for a water cotransport function of BBB GLUT1. A shift in transporter polarity characterized by increased luminal membrane GLUT1 is seen when BBB glucose transport is upregulated; but a greater abluminal membrane density is seen in the human BBB when GLUT1 is downregulated. PKC colocalizes with GLUT1 within these endothelial domains during up-and downregulation, suggesting that a PKC-mediated mechanism regulates human BBB glucose transporter expression. Occludin and claudin-5 (like other tight-junctional proteins) exhibit a restricted distribution, and are expressed solely within interendothelial clefts of the BBB. GFAP (glial fibrillary acidic protein) is uniformly expressed throughout the foot-processes and the entire astrocyte. But the microvascular-facing membranes of the glial processes that contact the basal laminae are also polarized, and their transporters may also redistribute within the astrocyte. Monocarboxylic acid transporter and water channel (Aquaporin-4) expression are enriched at the glial foot-process, and both undergo physiological modulation. We suggest that as transcytosis and efflux mechanisms generate interest as potential neurotherapeutic targets, electron microscopic confirmation of their site-specific expression patterns will continue to support the CNS drug discovery process.

show abstract

“…Astrocytes express all three isoforms of caveolins (Virgintino et al 2002), which play complex rolea that are not completely understood. Recently, we have reported that treatment of cultured astrocytes with ammonium as well as treatment of animals with urease up-regulates astroglial Cav-1 gene expression, which, in turn, increases membrane content of PTEN, inhibits PI3K/AKT signalling, and enhances GSK-3β activity (Wang et al 2016).…”

Section: Page 10 Of 27 Psychopharmacologymentioning

confidence: 99%

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Bai

Song

et al. 2017

Psychopharmacology

View full text Add to dashboard Cite

Here we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At lower concentrations fluoxetine down-regulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes. Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.

show abstract

Expression of caveolin-1 in human brain microvessels

Cited by 96 publications

References 40 publications

Diphtheria Toxin Mutant CRM197-Mediated Transcytosis across Blood–Brain Barrier In Vitro

Diphtheria Toxin Mutant CRM197-Mediated Transcytosis across Blood–Brain Barrier In Vitro

Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Contact Info

Product

Resources

About