Studies on pregnancy-associated plasma protein A

Gore, Christine Helen (1982) Studies on pregnancy-associated plasma protein A. PhD thesis, University of Glasgow.

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Abstract

Various pregnancy associated proteins are detected in maternal serum during pregnancy, some of which are also present at low levels in non-pregnancy serum. A review of the literature has been made and the following conclusions have been drawn. Pregnancy associated proteins are synthesised by a variety of maternal, fetal and placental tissues. Both steroid and proteinaceous hormones are produced, together with enzymes and other protein. The functions of many of these proteins have still to be determined. In vitro investigations have suggested that some of these proteins may be involved in haemostasis and in immune suppressions. However, their precise roles in the complex and sensitive immunobiological equilibrium that exists between maternal and fetal tissues during pregnancy, has not been established. Some placental proteins have been used, to varying degrees of success, to monitor pregnancy and fetal well-being. Others have proved invaluable for monitoring malignancies, metastasis and the recurrence of tumours after treatment. A better understanding of the function of pregnancy specific proteins would significantly increase their clinical and practical usefulness. Pregnancy-associated plasma protein A (PAPP-A) one of the more recently discovered placental proteins, has similar physicochemical properties to the serum protease inhibitor alpha-2-macroglobulin (alpha2M). It has been suggested that these two proteins may be homologues (or analogues) as has been observed for other pregnancy associated proteins. A functional homology has also been suggested for these two proteins. Histological staining studies by various workers have localised PAPP-A to the syncytiotropl)oblast, the villous cytotrophoblast, the utero-placental fibrinoid and in reticular fibres around uterine decidual cellso This distribution is similar to that observed for the high molecular weight glycoprotein fibronectin" Tissue from the utero-placental and chorionic plates synthesised both 35S-labelled PAPP-A and fibronectin after one week of culturing. The purpose of this investigation was to develop a purification protocol for the production of physiologically active PAPP-A, and to further compare alpha2M and PAPP-A both physicochemically and functionallyo The following results were obtained. The neutral carbohydrate content of PAPP-A, purified by positive affinity chromatography, was determined. PAPP-A contained a mean neutral carbohydrate content of 12.97%, the value obtained for alpha2M was 3.9%. Only 4.8% of the protein in a solution of purified PAPP-A was precipitable in 12.5% trichloroacetic acid, compared with 53.9% precipitation for a solution of alpha2M. However, PAPP-A was insoluble in 5% phosphotungstic acid in 2M HCl. These results are consistent with the relatively high total carbohydrate content observed for PAPP-A (19.2%). PAPP-A was obtained in an enriched state under mild purification conditions, involving Cibacron blue dye-ligand chromatography, negative antibody affinity chromatography and gel filtration. The product was a mixture of PAPP-A and alpha2M (the PAPP-A enriched preparation or PEP). The ability of these proteins to bind 125I-trypsin and 125I-plasmin was studied. In contrast to previous studies, there was no evidence that PAPP-A bound proteases, and on incubation with an equimolar (approx) concentration of trypsin 125I-PAPP-A degradation was observed. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Roger Sutcliffe
Keywords: Molecular biology, Obstetrics
Date of Award: 1982
Depositing User: Enlighten Team
Unique ID: glathesis:1982-72786
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06
URI: http://theses.gla.ac.uk/id/eprint/72786

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