Samuel Parry1, Jian Zhang. 1. Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Abstract
OBJECTIVE: We studied the role of multidrug resistance proteins in regulating transplacental transmission of corticosteroids and protease inhibitors. STUDY DESIGN: We performed quantitative polymerase chain reaction and FACS analyses to study MDR1 (encodes P-glycoprotein) and MRP-1 expression in extravillous (HTR-8/SVneo) and villous (BeWo) trophoblast cells treated with saquinavir, a multidrug resistance protein substrate. We measured H3-dexamethasone and H3-ritonavir transfer across confluent, syncytialized BeWo cells before and after treatment with agents that inhibit multidrug resistance proteins. RESULTS: Compared with baseline expression, messenger RNA and protein levels were increased significantly in trophoblast cells after treatment with saquinavir. H3-dexamethasone and H3-ritonavir levels increased in BeWo cells after treatment with anti-P-glycoprotein antibodies or cyclosporine A. Transfer of H3-labeled drugs from the apical (eg, maternal) to basolateral (eg, fetal) side of the syncytialized BeWo cell monolayer was increased significantly when cells were pretreated with anti-P-glycoprotein antibodies. CONCLUSION: Multidrug resistance proteins regulate drug levels in trophoblast cells and may mediate transmission of therapeutic agents across the placenta.
OBJECTIVE: We studied the role of multidrug resistance proteins in regulating transplacental transmission of corticosteroids and protease inhibitors. STUDY DESIGN: We performed quantitative polymerase chain reaction and FACS analyses to study MDR1 (encodes P-glycoprotein) and MRP-1 expression in extravillous (HTR-8/SVneo) and villous (BeWo) trophoblast cells treated with saquinavir, a multidrug resistance protein substrate. We measured H3-dexamethasone and H3-ritonavir transfer across confluent, syncytialized BeWo cells before and after treatment with agents that inhibit multidrug resistance proteins. RESULTS: Compared with baseline expression, messenger RNA and protein levels were increased significantly in trophoblast cells after treatment with saquinavir. H3-dexamethasone and H3-ritonavir levels increased in BeWo cells after treatment with anti-P-glycoprotein antibodies or cyclosporine A. Transfer of H3-labeled drugs from the apical (eg, maternal) to basolateral (eg, fetal) side of the syncytialized BeWo cell monolayer was increased significantly when cells were pretreated with anti-P-glycoprotein antibodies. CONCLUSION: Multidrug resistance proteins regulate drug levels in trophoblast cells and may mediate transmission of therapeutic agents across the placenta.
Authors: Gevdeep Bhabra; Aman Sood; Brenton Fisher; Laura Cartwright; Margaret Saunders; William Howard Evans; Annmarie Surprenant; Gloria Lopez-Castejon; Stephen Mann; Sean A Davis; Lauren A Hails; Eileen Ingham; Paul Verkade; Jon Lane; Kate Heesom; Roger Newson; Charles Patrick Case Journal: Nat Nanotechnol Date: 2009-12 Impact factor: 39.213
Authors: Caroline E Dunk; Jane J Pappas; Phetcharawan Lye; Mark Kibschull; Mohsen Javam; Enrrico Bloise; Stephen J Lye; Moshe Szyf; Stephen G Matthews Journal: J Cell Mol Med Date: 2018-09-05 Impact factor: 5.310