MDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72677
Title:
MDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction.
Authors:
Atkinson, Diane E; Sibley, C P; Fairbairn, Leslie J; Greenwood, Susan L
Abstract:
This study investigates P-gp activity in placental villous fragments and the possibility of upregulating its expression and function by retroviral transduction. In fresh fragments, cyclosporin A caused a significant increase in 3H-vinblastine accumulation (187+/-48% at 180 min n=4), consistent with multi-drug resistance activity. After 7 days in culture, villous fragments showed a similar increase in 3H-vinblastine accumulation (143+/-10% at 180 min n=4), which was not significantly different from that in fresh tissue. Following transduction, immunohistochemistry revealed increased P-gp expression. However, the distribution of the protein differed from that in controls, with P-gp being located throughout the tissue as opposed to the normal specific location on the maternal facing plasma membrane. Transduced explants showed a significantly larger increase in 3H-vinblastine accumulation in the presence of cyclosporin A than control explants (245+/-15.5% at 180 min, n=4), suggesting reduced capacity to efflux vinblastine. This study demonstrates P-gp activity in intact placental tissue which is maintained in explant culture. Retroviral transduction of P-gp to such tissue leads to increased but undirected expression of the protein. The consequent increased activity at sites such as the basal, fetal facing, plasma membrane probably explains the increased substrate accumulation within the tissue.
Affiliation:
Academic Unit of Child Health, Division of Human Development, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, UK. diane.e.atkinson@man.ac.uk
Citation:
MDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction., 27 (6-7):707-14 Placenta
Journal:
Placenta
Issue Date:
7-Jul-2009
URI:
http://hdl.handle.net/10541/72677
DOI:
10.1016/j.placenta.2005.06.008
PubMed ID:
16122788
Type:
Article
Language:
en
ISSN:
0143-4004
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAtkinson, Diane E-
dc.contributor.authorSibley, C P-
dc.contributor.authorFairbairn, Leslie J-
dc.contributor.authorGreenwood, Susan L-
dc.date.accessioned2009-07-07T09:59:32Z-
dc.date.available2009-07-07T09:59:32Z-
dc.date.issued2009-07-07T09:59:32Z-
dc.identifier.citationMDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction., 27 (6-7):707-14 Placentaen
dc.identifier.issn0143-4004-
dc.identifier.pmid16122788-
dc.identifier.doi10.1016/j.placenta.2005.06.008-
dc.identifier.urihttp://hdl.handle.net/10541/72677-
dc.description.abstractThis study investigates P-gp activity in placental villous fragments and the possibility of upregulating its expression and function by retroviral transduction. In fresh fragments, cyclosporin A caused a significant increase in 3H-vinblastine accumulation (187+/-48% at 180 min n=4), consistent with multi-drug resistance activity. After 7 days in culture, villous fragments showed a similar increase in 3H-vinblastine accumulation (143+/-10% at 180 min n=4), which was not significantly different from that in fresh tissue. Following transduction, immunohistochemistry revealed increased P-gp expression. However, the distribution of the protein differed from that in controls, with P-gp being located throughout the tissue as opposed to the normal specific location on the maternal facing plasma membrane. Transduced explants showed a significantly larger increase in 3H-vinblastine accumulation in the presence of cyclosporin A than control explants (245+/-15.5% at 180 min, n=4), suggesting reduced capacity to efflux vinblastine. This study demonstrates P-gp activity in intact placental tissue which is maintained in explant culture. Retroviral transduction of P-gp to such tissue leads to increased but undirected expression of the protein. The consequent increased activity at sites such as the basal, fetal facing, plasma membrane probably explains the increased substrate accumulation within the tissue.en
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshChorionic Villi-
dc.subject.meshCyclosporine-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshHumans-
dc.subject.meshOrgan Culture Techniques-
dc.subject.meshP-Glycoprotein-
dc.subject.meshPregnancy-
dc.subject.meshRetroviridae-
dc.subject.meshTransduction, Genetic-
dc.subject.meshUp-Regulation-
dc.subject.meshVinblastine-
dc.titleMDR1 P-gp expression and activity in intact human placental tissue; upregulation by retroviral transduction.en
dc.typeArticleen
dc.contributor.departmentAcademic Unit of Child Health, Division of Human Development, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, UK. diane.e.atkinson@man.ac.uken
dc.identifier.journalPlacentaen

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