Linked Life Data

11816711

Source:http://linkedlifedata.com/resource/pubmed/id/11816711

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-12-5
pubmed:abstractText
Plasma factor XIII (plasma protransglutaminase) circulates as an A2B2 tetramer bound to the gamma' variant chains of fibrinogen "2". During clotting the A subunits of fXIII are cleaved by thrombin to form fXIIIa (transglutaminase) and in the presence of calcium ions, activated A2* subunits dissociate from the B subunits. When purified plasma fXIII or recombinant cellular factor XIII (A2) was incubated with fibrinogen in the presence of calcium ions (> or =50 microM) a non-synerizing gel formed concomitant with formation of gamma dimers, followed by Agamma polymers, and eventually gamma trimers and gamma tetramers. As is the case of fXIIIa, the fXIII-mediated crosslinking rate was enhanced in the presence of thiols. After an initial lag period, fXIII catalyzed fibrinogen crosslinking at approximately 75% of the rate of fXIIIa under typical crosslinking conditions (100 Loewy u/ml, 5 mM CaCl2 & 500 microM DTT). Fibrin was crosslinked about 8 times more rapidly by fXIII than was fibrinogen, and after an initial lag period fXIII crosslinked fibrin at nearly the same rate as fXIIIa. Substituting plasma for purified fXIII as the source for fXIII resulted in robust fibrinogen crosslinking activity. In contrast to the high level of fXIII-mediated crosslinking activity observed with fibrinogen or fibrin as substrates, when transglutamination was measured using cadaverine incorporation into casein, fXIII was 30-fold less active than fXIIIa. Thus, factor XIII displays constitutive enzymatic activity with respect to fibrinogen and fibrin. The results further indicate that uncleaved fXIII in plasma provides a potent source of readily available crosslinking activity in clotting blood. Fibrinogen 2, whose gamma'chains bind fXIII B subunits, was crosslinked 3.5 times more slowly by fXIII than was fibrinogen 1 (lacking gamma' chains), suggesting that complex formation between fibrinogen 2 and plasma fXIII plays a significant role in down-regulating potential plasma fXIII-mediated crosslinking activity. Since fibrin is a considerably better substrate for fXIII than is fibrinogen, the rate at which crosslinking takes place in a fibrinogen-containing plasma environment is much lower than it would be if fibrin were present.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1221-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Protransglutaminase (factor XIII) mediated crosslinking of fibrinogen and fibrin.
pubmed:affiliation
Department of Biomedical Sciences, College of Health Sciences, Marquette University, Milwaukee, WI, USA. kevin.siebenlist@marquette.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.