Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy
Article
Hills, F., Iles, R. and Sullivan, M. 2013. Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy. Journal of Perinatal Medicine. 41 (3), pp. 241-249. https://doi.org/10.1515/jpm-2012-0086
Type | Article |
---|---|
Title | Differential proteolysis of insulin-like growth factor binding protein-1 (IGFBP-1) in pregnancy |
Authors | Hills, F., Iles, R. and Sullivan, M. |
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. |
Keywords | Amniotic fluid; IGF binding protein-1; insulin-like growth factor; proteolysis |
Research Group | Centre for Investigative and Diagnostic Oncology |
Biomarkers for Cancer group | |
Reproductive Biology group | |
Publisher | De Gruyter |
Journal | Journal of Perinatal Medicine |
ISSN | 0300-5577 |
Publication dates | |
May 2013 | |
Publication process dates | |
Deposited | 15 Mar 2013 |
Accepted | 16 Oct 2012 |
Output status | Published |
Publisher's version | |
Digital Object Identifier (DOI) | https://doi.org/10.1515/jpm-2012-0086 |
Language | English |
https://repository.mdx.ac.uk/item/83y8w
Download files
Restricted files
Accepted author manuscript
55
total views11
total downloads1
views this month0
downloads this month