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PMID:10340997

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Citation

He, S, Lin, YL and Liu, YX (1999) Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol. Hum. Reprod. 5:513-9

Abstract

Protein C inhibitor (PCI) has been found in seminal plasma and is considered to protect intact surrounding cells and seminal plasma proteins from possible proteolytic damage. In the present study, we showed that although the antigenic levels of PCI in two seminal plasma samples from patients with infertility were normal or slightly elevated, their inhibitory activities toward urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) were absent. In contrast, uPA and tPA proteolytic activities in these two samples were 20-60-fold higher than that from normal volunteers. A time-course analysis of PCI-uPA complex formation showed that >80% of the complex had been formed within 15 min in normal seminal plasma in the presence of heparin, compared with the total complex formed after 150 min incubation, whereas no response to heparin stimulation was observed in the assays with the two patient samples. Similarly, >90% of PCI-tPA complex was formed after 30 min of heparin stimulation in normal seminal plasma but no response was observed in the two patient samples. Kinetic assays of PCI inhibitory function in the presence of activated protein C (APC) showed that PCI inhibitory activity in the two patient samples was absent and not stimulated by heparin. Western blotting also showed that most of the intact PCI molecules, in normal samples, formed complexes with either uPA or tPA but there was no complex formed in one of the two patient samples and very little complex was observed in the other, suggesting that PCI in the two patient samples is inactive. These results suggest that the presence of functionally inactive PCI in seminal plasma may be associated with infertility.

Links

PubMed

Keywords

Adult; Blotting, Western; Electrophoresis, Polyacrylamide Gel/methods; Heparin/pharmacology; Humans; Infertility, Male/metabolism; Kinetics; Male; Protein C Inhibitor/analysis; Protein C Inhibitor/metabolism; Reference Values; Semen/drug effects; Semen/metabolism; Time Factors; Tissue Plasminogen Activator/metabolism; Urokinase-Type Plasminogen Activator/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:UROK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05154

F

Seeded From UniProt

complete

HUMAN:TPA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05154

F

Seeded From UniProt

complete

HUMAN:IPSP

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:IPSP

enables

GO:0002020: protease binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P00750

F

Seeded From UniProt

complete

HUMAN:IPSP

enables

GO:0002020: protease binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P00749

F

Seeded From UniProt

complete

HUMAN:IPSP

enables

GO:0004867: serine-type endopeptidase inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:IPSP

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:IPSP

part_of

GO:0036026: protein C inhibitor-PLAT complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:IPSP

part_of

GO:0036027: protein C inhibitor-PLAU complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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