scholarly journals OC23.02: Pregnancy-associated plasma protein A levels and neonatal complications in post-term pregnancies

2012 ◽  
Vol 40 (S1) ◽  
pp. 48-48
Author(s):  
A. R. Zizzo ◽  
I. Kirkegaard ◽  
T. B. Heniksen ◽  
N. Uldbjerg
Keyword(s):  
Plasma Protein ◽  
Protein A ◽  
Neonatal Complications

scholarly journals 963 Pregnancy-Associated Plasma Protein a Levels and Neonatal Complications in Post-Term Pregnancies

2012 ◽  
Vol 97 (Suppl 2) ◽  
pp. A275-A275
Author(s):  
A. Zizzo ◽  
I. Kirkegaard ◽  
T. Henriksen ◽  
N. Uldbjerg
Keyword(s):  
Plasma Protein ◽  
Protein A ◽  
Neonatal Complications

Pregnancy-associated plasma protein A levels and neonatal complications in post-date pregnancies

2013 ◽  
Vol 33 (10) ◽  
pp. 965-972 ◽  
Author(s):  
Anne R. Zizzo ◽  
Ida Kirkegaard ◽  
Tine B. Henriksen ◽  
Niels Ulbjerg
Keyword(s):  
Plasma Protein ◽  
Protein A ◽  
Neonatal Complications

scholarly journals Quantification of Proteolytically Active Pregnancy-Associated Plasma Protein-A with an Assay Based on Quenched Fluorescence

2007 ◽  
Vol 53 (5) ◽  
pp. 947-954 ◽  
Author(s):  
Claus Gyrup ◽  
Michael Christiansen ◽  
Claus Oxvig
Keyword(s):  
Proteolytic Activity ◽  
Plasma Protein ◽  
Basic Protein ◽  
Biological Function ◽  
Limit Of Detection ◽  
Protein A ◽  
Maternal Serum ◽  
Serum Samples ◽  
A Subunit ◽  
Eosinophil Major Basic Protein

Abstract Background: Maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome. In pregnancy, PAPP-A primarily circulates as a covalent 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. At term, however, ∼1% of PAPP-A exists as an active, uncomplexed dimer with proteolytic activity directed specifically toward insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5. No assays have been developed that allow quantification of PAPP-A proteolytic activity. Methods: We developed a sensitive and specific immunocapture assay for PAPP-A activity based on intramolecular quenched fluorescence. We used a 26-residue synthetic peptide derived from IGFBP-4 in which specific positions on each side of the PAPP-A cleavage site were substituted with 3-nitrotyrosine and o-aminobenzoic acid. Results: The assay detected the activity of recombinant PAPP-A as well as PAPP-A in serum samples from pregnant women. The limit of detection (mean signal of blank plus 3 SD) of the active PAPP-A subunit was 13 pmol/L, and the intra- and interassay CVs were <10% and <15%, respectively. Interestingly, the fraction of active PAPP-A decreased gradually from week 7 to week 19 of pregnancy. Conclusions: This method allows the measurement of PAPP-A enzymatic activity and because of its specificity it is relevant to the study of the biological function of PAPP-A. The method may also be useful in the diagnosis of pregnancy disorders.

scholarly journals Studies on regulation of IGF (insulin-like growth factor)-binding protein (IGFBP) 4 proteolysis by pregnancy-associated plasma protein-A (PAPP-A) in cells treated with phorbol ester

2004 ◽  
Vol 379 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Arun S. SIVANANDAM ◽  
Subburaman MOHAN ◽  
Hirohito KITA ◽  
Sanjay KAPUR ◽  
Shin-Tai CHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Proteolytic Activity ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Fold Reduction ◽  
Sds Page ◽  
Eosinophil Major Basic Protein

PAPP-A (pregnancy-associated plasma protein-A) is produced by hSFs (human skin fibroblasts) and hOBs (human osteoblasts) and enhances the mitogenic activity of IGFs (insulin-like growth factors) by degradation of IGFBP-4 (insulin-like growth factor-binding protein 4). PKC (protein kinase C) activation in these cells led to reduction in IGFBP-4 proteolysis. This study was undertaken to determine the mechanism by which activation of PKC suppresses IGFBP-4 proteolysis. Treatment of hSFs/hOBs with TPA (PMA; 100 nM) reduced IGFBP-4 proteolysis without significantly decreasing the PAPP-A level in the CM (conditioned medium). Immunodepletion of the proform of eosinophil major basic protein (proMBP), a known PAPP-A inhibitor, from CM of TPA-treated cells (TPA CM) failed to increase IGFBP-4 proteolytic activity. Transduction of hSFs with proMBP retrovirus increased the concentration of proMBP up to 30 ng/ml and led to a moderate reduction in IGFBP-4 proteolysis. In contrast, TPA treatment blocked IGFBP-4 proteolysis but failed to induce a detectable amount of proMBP in the CM. While proMBP overexpression led to the formation of a covalent proMBP–PAPP-A complex and reduced the migration of PAPP-A on SDS/PAGE, TPA treatment dose- and time-dependently increased the conversion of a ≈470 kDa PAPP-A form (PAPP-A470) to a ≈400 kDa PAPP-A form (PAPP-A400). Since unreduced PAPP-A400 co-migrated with the 400 kDa recombinant PAPP-A homodimer and since PAPP-A monomers from reduced PAPP-A470 and PAPP-A400 co-migrated on SDS/PAGE, conversion of PAPP-A470 to PAPP-A400 is unlikely to be caused by proteolytic cleavage of PAPP-A. Consistent with the data showing that the increase in the ratio of PAPP-A400/PAPP-A470 is correlated with the extent of reduction in IGFBP-4 proteolysis, partially purified PAPP-A400 exhibited a 4-fold reduction in IGFBP-4 proteolytic activity compared with PAPP-A470. These data suggest that a novel mechanism, namely conversion of PAPP-A470 to the less-active PAPP-A400, could account for the TPA-induced suppression of PAPP-A activity.

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