Linked Life Data

9275081

Source:http://linkedlifedata.com/resource/pubmed/id/9275081

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1997-9-18
pubmed:abstractText
The presence of a proteolytic activity in sera from pregnant humans and rodents capable of degrading insulin-like growth factor binding protein-3 (IGFBP-3) has been known for some time. However, the identity of this activity has remained elusive. We have attempted to purify the IGFBP-3 protease activity from pregnant human serum (PHS) using the degradation of 125I-IGFBP-3 as a marker. Following ammonium sulfate precipitation of PHS and further enrichment of active fractions by ion-exchange, protein-A Sepharose, and size-exclusion chromatography, a protease of approximately 70-90 kDa was isolated and subjected to N-terminal analysis. The N-terminal sequence was consistent with plasminogen, a known fibrinolytic enzyme. To further characterize the IGFBP-3 protease activities in both PHS and nonpregnant human serum (NHS), aliquots of serum were first enriched by polyethylene glycol-precipitation and subjected to size-exclusion chromatography. The size-separated fractions were then incubated with 125I-IGFBP-3, and proteolytic activity was measured. PHS contained two separate proteases (>150 kDa and 70-90 kDa), whereas NHS contained only one (70-90 kDa) that had a inhibitor profile similar to plasmin. However, inhibitors of plasmin had no effect on the activity of the >150-kDa protease. Plasminogen activators (PAs) greatly increased the activity of the 70- to 90-kDa protease, but had little effect on the >150-kDa protease activity. Addition of PAs greatly increased the ability of NHS to proteolyze IGFBP-3. In contrast, the ability of plasminogen-depleted plasma to degrade 125I-IGFBP-3 was not affected by the addition of PAs. Both urokinase and tissue-type PA had the ability to proteolyze IGFBP-3 and were, in contrast to the >150-kDa protease activity, inhibited by the specific PA inhibitor D-PHE-PRO-ARG chloromethyl ketone. The present data suggest that sera has the ability to proteolyze IGFBP-3, and that this ability, as demonstrated by NHS, can be regulated by protease inhibitors and PAs. In addition, PHS does indeed contain an unique IGFBP-3 protease activity that is not present in NHS, and its identity is unknown at this time.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Edetic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding..., http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activators, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Inactivators, http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Tissue Plasminogen Activator, http://linkedlifedata.com/resource/pubmed/chemical/Urokinase-Type Plasminogen Activator, http://linkedlifedata.com/resource/pubmed/chemical/Zinc, http://linkedlifedata.com/resource/pubmed/chemical/insulin-like growth factor binding...
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3912-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Human pregnancy serum contains at least two distinct proteolytic activities with the ability to degrade insulin-like growth factor binding protein-3.
pubmed:affiliation
Department of Women and Child Health, Karolinska Hospital and Institute, Stockholm, Sweden. peter.bang@netg.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't