title: In vitro and in vivo study of dolichyl phosphate on the efflux activity of P-glycoprotein at the blood-brain barrier.
abstract: It has been commonly recognized that accumulated amyloid-β (Aβ) in the brain plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Since the deficiency of the P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in AD may aggravate Aβ deposition and the P-gp reversal agents display lower selectivity of the action, to selectively restore activity of the efflux pump is eagerly required. This study was designed to investigate the influence of dolichyl-phosphate (dolichyl-P) on the P-gp at the BBB. The results revealed that treatment with dolichyl-P increased transendothelial transfer of Rhodamine123 (Rh123) and Aβ42 from the apical compartment to the basolateral compartment but reduced that from the basolateral compartment to the apical compartment in the co-culture of rat brain microvessel endothelial cells (rBMECs) and astrocytes, down regulated P-gp expression in rBMECs and significantly elevated content of Rh123 in rat cortex and hippocampus tissues. The present results implied that accumulated dolichyl-P in the brain may exert an important role in the depression of the P-gp at the BBB, which may suggest valuable clues to promote function of the pump at the BBB in AD.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, China. Electronic address: jibiansheng2005@126.com.
authors.forename: Bian-Sheng
authors.initials: BS
authors.lastname: Ji
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: He
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D062507:Claudin-5 / Q000378:metabolism; D018920:Coculture Techniques; D004288:Dolichol Phosphates / Q000494:pharmacology*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016229:Amyloid beta-Peptides; D062507:Claudin-5; D004288:Dolichol Phosphates; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C028306:dolichol monophosphate
keywords: Alzheimer's disease; Blood–brain barrier; Dolichyl phosphate; P-glycoprotein