Literature DB >> 21487415

Activating PKC-β1 at the blood-brain barrier reverses induction of P-glycoprotein activity by dioxin and restores drug delivery to the CNS.

Xueqian Wang1, Brian T Hawkins, David S Miller.   

Abstract

Upregulation of blood-brain barrier (BBB) P-glycoprotein expression causes central nervous system (CNS) pharmacoresistance. However, activation of BBB protein kinase C-β1 (PKC-β1) rapidly reduces basal P-glycoprotein transport activity. We tested whether PKC-β1 activation would reverse CNS drug resistance caused by dioxin acting through aryl hydrocarbon receptor. A selective PKC-β1 agonist abolished the increase in P-glycoprotein activity induced by dioxin in isolated rat brain capillaries and reversed the effect of dioxin on brain uptake of verapamil in dioxin-dosed rats. Thus, targeting BBB PKC-β1 may be an effective strategy to improve drug delivery to the brain, even in drug-resistant individuals.

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Year:  2011        PMID： 21487415      PMCID： PMC3130326          DOI： 10.1038/jcbfm.2011.44

Source DB:  PubMed          Journal:  J Cereb Blood Flow Metab        ISSN： 0271-678X            Impact factor:   6.200


  15 in total

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Authors:  Anika M S Hartz; Björn Bauer; Gert Fricker; David S Miller
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3.  Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases.

Authors:  B T Hawkins; T F Lundeen; K M Norwood; H L Brooks; R D Egleton
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4.  Constitutive androstane receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier.

Authors:  Xueqian Wang; Destiny B Sykes; David S Miller
Journal:  Mol Pharmacol       Date:  2010-06-14       Impact factor: 4.436

5.  Activation of PKC isoform beta(I) at the blood-brain barrier rapidly decreases P-glycoprotein activity and enhances drug delivery to the brain.

Authors:  Robert R Rigor; Brian T Hawkins; David S Miller
Journal:  J Cereb Blood Flow Metab       Date:  2010-03-03       Impact factor: 6.200

6.  Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier.

Authors:  Björn Bauer; Anika M S Hartz; Gert Fricker; David S Miller
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7.  Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1.

Authors:  Anika M S Hartz; Björn Bauer; Gert Fricker; David S Miller
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Review 8.  Functional and structural comparison of PXR and CAR.

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  9 in total

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Journal:  FASEB J       Date:  2012-12-04       Impact factor: 5.191

4.  Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain.

Authors:  Ronald E Cannon; John C Peart; Brian T Hawkins; Christopher R Campos; David S Miller
Journal:  Proc Natl Acad Sci U S A       Date:  2012-09-04       Impact factor: 11.205

5.  Enzastaurin inhibits ABCB1-mediated drug efflux independently of effects on protein kinase C signalling and the cellular p53 status.

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Review 6.  Host-microbiome interactions: the aryl hydrocarbon receptor and the central nervous system.

Authors:  Hae Ung Lee; Zachary E McPherson; Bryan Tan; Agata Korecka; Sven Pettersson
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Review 7.  Enteric Microbiota⁻Gut⁻Brain Axis from the Perspective of Nuclear Receptors.

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Review 8.  Host-microbiota interactions: The aryl hydrocarbon receptor in the acute and chronic phases of cerebral ischemia.

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9.  David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.

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Journal:  Fluids Barriers CNS       Date:  2020-09-14
  9 in total

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