FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892528183> ?p ?o ?g. }

• W2892528183 endingPage "2060" @default.
• W2892528183 startingPage "2049" @default.
• W2892528183 abstract "Objective Nuclear receptors and cytochrome P450 (CYP) regulate hepatic metabolism of several drugs. Nuclear receptors are expressed at the neurovascular unit of patients with drug-resistant epilepsy. We studied whether glucocorticoid receptor (GR) silencing or inhibition in human epileptic brain endothelial cells (EPI-ECs) functionally impacts drug bioavailability across an in vitro model of the blood-brain barrier (BBB) by CYP-multidrug transporter (multidrug resistance protein 1, MDR1) mechanisms. Methods Surgically resected brain specimens from patients with drug-resistant epilepsy, primary EPI-ECs, and control human brain microvascular endothelial cells (HBMECs) were used. Expression of GR, pregnane X receptor, CYP3A4, and MDR1 was analyzed pre- and post-GR silencing in EPI-ECs. Endothelial cells were co-cultured with astrocytes and seeded in an in vitro flow-based BBB model (DIV-BBB). Alternatively, the GR inhibitor mifepristone was added to the EPI-EC DIV-BBB. Integrity of the BBB was monitored by measuring transendothelial electrical resistance. Cell viability was assessed by glucose-lactate levels. Permeability of [3 H]sucrose and [14 C]phenytoin was quantified. CYP function was determined by measuring resorufin formation and oxcarbazepine (OXC) metabolism. Results Silencing and inhibition of GR in EPI-ECs resulted in decreased pregnane X receptor, CYP3A4, and MDR1 expression. GR silencing or inhibition did not affect BBB properties in vitro, as transendothelial electrical resistance and Psucrose were unaltered, and glucose metabolism was maintained. GR EPI-EC silencing or inhibition led to (1) increased Pphenytoin BBB permeability as compared to control; (2) decreased CYP function, indirectly evaluated by resorufin formation; (3) improved OXC bioavailability with increased abluminal (brain-side) OXC levels as compared to control. Significance Our results suggest that modulating GR expression in EPI-ECs at the BBB modifies drug metabolism and penetration by a mechanism encompassing P450 and efflux transporters. The latter could be exploited for future drug design and to overcome pharmacoresistance." @default.
• W2892528183 created "2018-10-05" @default.
• W2892528183 creator A5009404756 @default.
• W2892528183 creator A5013584913 @default.
• W2892528183 creator A5018257731 @default.
• W2892528183 creator A5022149512 @default.
• W2892528183 creator A5036239459 @default.
• W2892528183 creator A5072148725 @default.
• W2892528183 creator A5073521552 @default.
• W2892528183 creator A5078408270 @default.
• W2892528183 creator A5080549180 @default.
• W2892528183 date "2018-09-28" @default.
• W2892528183 modified "2023-10-14" @default.
• W2892528183 title "Modulation of glucocorticoid receptor in human epileptic endothelial cells impacts drug biotransformation in an in vitro blood–brain barrier model" @default.
• W2892528183 cites W1548840271 @default.
• W2892528183 cites W1549213315 @default.
• W2892528183 cites W1575158876 @default.
• W2892528183 cites W1591367548 @default.
• W2892528183 cites W1950472309 @default.
• W2892528183 cites W1965825054 @default.
• W2892528183 cites W1973722262 @default.
• W2892528183 cites W1977291679 @default.
• W2892528183 cites W1977607154 @default.
• W2892528183 cites W1977687035 @default.
• W2892528183 cites W1982531351 @default.
• W2892528183 cites W1984862370 @default.
• W2892528183 cites W1985748956 @default.
• W2892528183 cites W1991347149 @default.
• W2892528183 cites W1992339013 @default.
• W2892528183 cites W1994404120 @default.
• W2892528183 cites W2001745713 @default.
• W2892528183 cites W2015541518 @default.
• W2892528183 cites W2021271765 @default.
• W2892528183 cites W2021275669 @default.
• W2892528183 cites W2027058216 @default.
• W2892528183 cites W2029562489 @default.
• W2892528183 cites W2038541687 @default.
• W2892528183 cites W2047075745 @default.
• W2892528183 cites W2055929484 @default.
• W2892528183 cites W2069118421 @default.
• W2892528183 cites W2073313174 @default.
• W2892528183 cites W2074926131 @default.
• W2892528183 cites W2082844918 @default.
• W2892528183 cites W2084256007 @default.
• W2892528183 cites W2093401853 @default.
• W2892528183 cites W2101099825 @default.
• W2892528183 cites W2101314083 @default.
• W2892528183 cites W2110150574 @default.
• W2892528183 cites W2110552899 @default.
• W2892528183 cites W2124596819 @default.
• W2892528183 cites W2133057534 @default.
• W2892528183 cites W2140316884 @default.
• W2892528183 cites W2162205607 @default.
• W2892528183 cites W2172258081 @default.
• W2892528183 cites W2340178656 @default.
• W2892528183 cites W2441329213 @default.
• W2892528183 cites W2588019568 @default.
• W2892528183 cites W2588265708 @default.
• W2892528183 cites W2726666234 @default.
• W2892528183 cites W2739173143 @default.
• W2892528183 cites W2774698827 @default.
• W2892528183 cites W2802451112 @default.
• W2892528183 doi "https://doi.org/10.1111/epi.14567" @default.
• W2892528183 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6282717" @default.
• W2892528183 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30264400" @default.
• W2892528183 hasPublicationYear "2018" @default.
• W2892528183 type Work @default.
• W2892528183 sameAs 2892528183 @default.
• W2892528183 citedByCount "15" @default.
• W2892528183 countsByYear W28925281832019 @default.
• W2892528183 countsByYear W28925281832020 @default.
• W2892528183 countsByYear W28925281832021 @default.
• W2892528183 countsByYear W28925281832022 @default.
• W2892528183 countsByYear W28925281832023 @default.
• W2892528183 crossrefType "journal-article" @default.
• W2892528183 hasAuthorship W2892528183A5009404756 @default.
• W2892528183 hasAuthorship W2892528183A5013584913 @default.
• W2892528183 hasAuthorship W2892528183A5018257731 @default.
• W2892528183 hasAuthorship W2892528183A5022149512 @default.
• W2892528183 hasAuthorship W2892528183A5036239459 @default.
• W2892528183 hasAuthorship W2892528183A5072148725 @default.
• W2892528183 hasAuthorship W2892528183A5073521552 @default.
• W2892528183 hasAuthorship W2892528183A5078408270 @default.
• W2892528183 hasAuthorship W2892528183A5080549180 @default.
• W2892528183 hasBestOaLocation W28925281831 @default.
• W2892528183 hasConcept C169760540 @default.
• W2892528183 hasConcept C181199279 @default.
• W2892528183 hasConcept C185592680 @default.
• W2892528183 hasConcept C202751555 @default.
• W2892528183 hasConcept C203014093 @default.
• W2892528183 hasConcept C2778402981 @default.
• W2892528183 hasConcept C2780035454 @default.
• W2892528183 hasConcept C2780841215 @default.
• W2892528183 hasConcept C27881333 @default.
• W2892528183 hasConcept C529278444 @default.
• W2892528183 hasConcept C55493867 @default.
• W2892528183 hasConcept C59493245 @default.
• W2892528183 hasConcept C71924100 @default.

• next