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    ROLES OF SULFOTRANSFERASE ENZYMES IN TRANS-PLACENTAL DISPOSITION

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    Mitra_ku_0099D_10193_DATA_1.pdf (3.636Mb)
    Issue Date
    2009-01-28
    Author
    Mitra, Pallabi
    Publisher
    University of Kansas
    Format
    189 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Pharmaceutical Chemistry
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    The trophoblast cell layer constitutes the rate-determining barrier for trans-placental transfer. Several isoforms of the sulfotransferase enzymes are functional in placenta but there is only limited information available on the utility of cultured trophoblast cells for studying placental sulfation. We examined the expression and activities of four sulfotransferase isoforms (SULT1A1, SULT1A3, SULT1E1, and SULT2A1) in primary cytotrophoblast cells and the trophoblast-like BeWo cell line. These isoforms have been reported to be functional in human placenta. Our results indicated that the phenolic sulfotransferase isoforms, SULT1A1 and SULT1A3, are functional in BeWo, as well as in the primary cytotrophoblast cells. SULT2A1 and SULT1E1 are not functional in either cell type. We also found that chronic exposure to the industrial chemical bisphenol A inhibited SULT1A1 activity. A U-shaped dose-response curve was observed with inhibition (~30-40%) being observed only at intermediate concentrations (10-100 nM). These results suggested that trophoblast cells may be used as a suitable in vitro tool to determine the effect of endogenous or exogenous substances on placental sulfotransferase activity. Altered metabolic activity has the chance of altering fetal exposure to drugs and other substances in the maternal circulation. Studies performed in BeWo cells also suggested that one of the roles of the placental efflux transporters is the elimination of sulfate metabolites. The multidrug resistance-associated proteins (MRPs) played a major role in the elimination of 4-nitrophenyl sulfate and acetaminophen sulfate across the basolateral (fetal-facing) and apical (maternal-facing) trophoblast membranes respectively. The breast cancer resistance protein (BCRP) played a minor role in the elimination of these two sulfate conjugates across the apical membrane.
    URI
    http://hdl.handle.net/1808/6185
    Collections
    • Dissertations [4475]
    • Pharmaceutical Chemistry Dissertations and Theses [141]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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