PMID- 22723979
OWN - NLM
STAT- MEDLINE
DCOM- 20121212
LR  - 20220317
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 6
DP  - 2012
TI  - Interaction of protein C inhibitor with the type II transmembrane serine protease 
      enteropeptidase.
PG  - e39262
LID - 10.1371/journal.pone.0039262 [doi]
LID - e39262
AB  - The serine protease inhibitor protein C inhibitor (PCI) is expressed in many 
      human tissues and exhibits broad protease reactivity. PCI binds 
      glycosaminoglycans and certain phospholipids, which modulate its inhibitory 
      activity. Enteropeptidase (EP) is a type II transmembrane serine protease mainly 
      found on the brush border membrane of epithelial cells in the duodenum, where it 
      activates trypsinogen to initiate the digestion of food proteins. Some active EP 
      is also present in duodenal fluid and has been made responsible for causing 
      pancreatitis in case of duodeno-pancreatic reflux. Together with its substrate 
      trypsinogen, EP is furthermore present in the epidermis and in some cancer cells. 
      In this report, we show that PCI inhibited EP with an apparent 2nd order rate 
      constant of 4.48 x 10(4) M(-1) s(-1). Low molecular weight (LMWH) and 
      unfractionated heparin (UFH) slightly reduced the inhibitory effect of PCI. The 
      SI (stoichiometry of inhibition) value for the inhibition of EP by PCI was 10.8 
      in the absence and 17.9 in the presence of UFH (10 U/ml). By inhibiting trypsin, 
      chymotrypsin, and additionally EP, PCI might play a role in the protection of the 
      pancreas from autodigestion. Furthermore the interaction of PCI with EP may 
      influence the regulation of epithelial differentiation.
FAU - Prohaska, Thomas A
AU  - Prohaska TA
AD  - Department of Vascular Biology and Thrombosis Research, Center for Physiology and 
      Pharmacology, Medical University of Vienna, Vienna, Austria.
FAU - Wahlmuller, Felix C
AU  - Wahlmuller FC
FAU - Furtmuller, Margareta
AU  - Furtmuller M
FAU - Geiger, Margarethe
AU  - Geiger M
LA  - eng
GR  - P 20386/FWF_/Austrian Science Fund FWF/Austria
GR  - P 22792/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120619
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antithrombins)
RN  - 0 (Protein C Inhibitor)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 0 (Serpins)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.9 (Enteropeptidase)
SB  - IM
MH  - Animals
MH  - Antithrombins/metabolism/pharmacology
MH  - Cattle
MH  - Dose-Response Relationship, Drug
MH  - Enteropeptidase/antagonists & inhibitors/*metabolism
MH  - Heparin/pharmacology
MH  - Humans
MH  - Mice
MH  - Protein Binding
MH  - Protein C Inhibitor/*metabolism/pharmacology
MH  - Serine Proteinase Inhibitors/*metabolism/pharmacology
MH  - Serpins/metabolism/pharmacology
PMC - PMC3378520
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/06/23 06:00
MHDA- 2012/12/13 06:00
PMCR- 2012/06/19
CRDT- 2012/06/23 06:00
PHST- 2012/03/30 00:00 [received]
PHST- 2012/05/22 00:00 [accepted]
PHST- 2012/06/23 06:00 [entrez]
PHST- 2012/06/23 06:00 [pubmed]
PHST- 2012/12/13 06:00 [medline]
PHST- 2012/06/19 00:00 [pmc-release]
AID - PONE-D-12-09182 [pii]
AID - 10.1371/journal.pone.0039262 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(6):e39262. doi: 10.1371/journal.pone.0039262. Epub 2012 Jun 19.