Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy

Hills, Frank, Iles, Ray K. and Sullivan, Mark H. (2013) Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. Journal of Perinatal Medicine, 41 (3). pp. 241-249. ISSN 0300-5577

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Abstract

The insulin-like growth factors and their binding proteins are important for placental and foetal growth. In this study, we have investigated the presence of proteolytic activity directed against insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. In addition, the effect of protease activity on IGFBP-1 immunoreactivity and IGF binding was characterised. 125I-IGFBP-1 was incubated with maternal and foetal serum, amniotic fluid and placental extracts. Breakdown of 125I-IGFBP-1 was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography. The size distribution of endogenous IGFBP-1 was determined by Western immunoblotting. Protease inhibitor studies characterised the proteolytic activity, and Western ligand blotting with 125I-IGF-I was used to determine IGF binding capacity of proteolysed IGFBP-1. Amniotic fluid samples collected after labour onset contained proteolytic activity that generated 12- and 19-kDa IGFBP-1 fragments that did not bind to 125I-IGF-I. This activity was not detected in amniotic fluid collected prior to labour onset or in other tissues. Activity was blocked by aprotinin, leupeptin, phenyl methyl sulphonyl fluoride, and Kunitz soybean trypsin inhibitor but not by ethylene diamine tetraacetic acid or pepstatin. Incubation of IGFBP-1 with trypsin generated fragments of a similar size to the amniotic fluid protease. In conclusion, we have demonstrated the presence in vivo of a trypsin-like proteolytic activity that alters the IGF-binding function of IGFBP-1 in pregnancy.

Item Type: Article
Keywords (uncontrolled): Amniotic fluid; IGF binding protein-1; insulin-like growth factor; proteolysis
Research Areas: A. > School of Health and Education > Centre for Investigative and Diagnostic Oncology
A. > School of Science and Technology > Natural Sciences
A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
A. > School of Science and Technology > Natural Sciences > Reproductive Biology group
Item ID: 10033
Useful Links:
Depositing User: Frank Hills
Date Deposited: 15 Mar 2013 15:16
Last Modified: 01 Jun 2019 17:19
URI: https://eprints.mdx.ac.uk/id/eprint/10033

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