Linked Life Data

12414897

Source:http://linkedlifedata.com/resource/pubmed/id/12414897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-11-4
pubmed:abstractText
Pregnancy-associated plasma protein-A (PAPP-A) is a product of the placenta and decidua and is secreted into the maternal circulation during human pregnancy. It recently has been identified as an IGF binding protein (IGFBP)-4 protease. Presumed functions at the maternal-fetal interface are to proteolyze IGFBP-4 and thus increase IGF bioavailability locally in the placenta, to promote IGF-II-mediated trophoblast invasion into the maternal decidua, and to modulate IGF regulation of steroidogenesis and glucose and amino acid transport in the villous. Herein, we have investigated the possibility that IGFBP-4 proteolysis may occur on the trophoblast cell membrane, presumably to increase local bioavailable IGF for interactions with cognate IGF membrane receptors. Human trophoblasts were cultured, trophoblast plasma membranes were isolated and solubilized, and IGFBP-4 protease activity and PAPP-A immunoreactivity in the solubilized plasma membrane fraction were investigated. IGFBP-4 protease activity was detected in solubilized human trophoblast membranes, resulting in cleavage of recombinant human IGFBP-4 into 18- and 14-kDa fragments, detected by Western immunoblot analysis. This protease activity was dependent on the presence of IGF-II, and its metal ion dependence was demonstrated by inhibition of the protease by the metal chelators, EDTA and EGTA. The presence of PAPP-A in solubilized human trophoblast membranes was demonstrated by Western immunoblotting. Trophoblast membrane PAPP-A had a relative molecular weight of approximately 200 kDa and comigrated on (reducing) SDS-PAGE with recombinant human PAPP-A and PAPP-A secreted into media conditioned by cultured human trophoblasts. IGFBP-4 protease activity was not detected after immunodepletion of PAPP-A from the trophoblast membrane fraction with PAPP-A polyclonal antibodies, suggesting the identity of the membrane-derived IGFBP-4 protease as PAPP-A. Immunocytochemistry revealed PAPP-A on the cell membrane and in the cytoplasm of human trophoblasts in culture. Together, these data demonstrate the presence of an IGF-II- and metal-dependent IGFBP-4 protease activity in human trophoblast plasma membranes, identified as PAPP-A, which is well situated to proteolyze IGFBP-4 at the maternal-placental interface to facilitate IGF action at the villous surface and/or the invading extravillous cytotrophoblast.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5235-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12414897-Antibodies, pubmed-meshheading:12414897-Blotting, Western, pubmed-meshheading:12414897-Cell Membrane, pubmed-meshheading:12414897-Cells, Cultured, pubmed-meshheading:12414897-Chelating Agents, pubmed-meshheading:12414897-Cytoplasm, pubmed-meshheading:12414897-Edetic Acid, pubmed-meshheading:12414897-Egtazic Acid, pubmed-meshheading:12414897-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12414897-Female, pubmed-meshheading:12414897-Humans, pubmed-meshheading:12414897-Immunohistochemistry, pubmed-meshheading:12414897-Insulin-Like Growth Factor Binding Protein 4, pubmed-meshheading:12414897-Insulin-Like Growth Factor II, pubmed-meshheading:12414897-Metalloendopeptidases, pubmed-meshheading:12414897-Molecular Weight, pubmed-meshheading:12414897-Peptide Fragments, pubmed-meshheading:12414897-Pregnancy, pubmed-meshheading:12414897-Pregnancy-Associated Plasma Protein-A, pubmed-meshheading:12414897-Recombinant Proteins, pubmed-meshheading:12414897-Trophoblasts
pubmed:year
2002
pubmed:articleTitle
Pregnancy-associated plasma protein A proteolytic activity is associated with the human placental trophoblast cell membrane.
pubmed:affiliation
Department of Gynecology and Obstetrics, Center for Research on Women's Health and Reproductive Medicine, Stanford University Medical Center, Stanford, CA 94305-5317, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.