Document Detail


Differences between neonates and adults in tissue-type-plasminogen activator (t-PA)-catalyzed plasminogen activation with various effectors and in carbohydrate sequences of fibrinogen chains.
MedLine Citation:
PMID:  11672579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our study investigates the effect of fetal and adult soluble fibrin (SF), fetal and adult fibrinogen Aalpha- and gamma-chains, as well as adult CNBr-fibrinogen fragments on tissue-type plasminogen activator (t-PA)-catalyzed plasminogen activation of both fetal and adult Glu-plasminogen types 1 and 2. In addition, we determined carbohydrate sequences of fetal and adult Bbeta- and gamma-chains by mass spectrometric analysis. In the absence of an effector, no substantial differences in the rate of plasmin formation could be seen between the fetal and adult plasminogen types. In the presence of an effector, both fetal Glu-plasminogen types revealed lower values for k(cat app) than the respective adult types. No differences could be seen in the values for K(m app). The resulting differences in catalytic efficiencies between the fetal and adult plasminogen types were much less than previously reported. No differences could be seen between fetal and adult effectors in stimulating t-PA-catalyzed plasminogen activation. Detailed analyses of the activation kinetics revealed a longer initial phase of slow plasmin formation of both fetal Glu-plasminogen types compared to their respective adult types, indicating a slower plasmin-induced modification of CNBr-fibrinogen fragments or SF by fetal plasmin. Mass spectrometric analysis of the N-glycans present on adult and fetal Bbeta- and gamma-fibrinogen chains showed the presence of a major monosialylated biantennary structure with lesser amounts of the disialylated form. In contrast to previous data, we conclude that catalytic efficiency of t-PA-catalyzed plasminogen activation in neonates is only slightly lower than in adults.
Authors:
M Ries; R L Easton; C Longstaff; M Zenker; P H Corran; H R Morris; A Dell; P J Gaffney
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Thrombosis research     Volume:  103     ISSN:  0049-3848     ISO Abbreviation:  Thromb. Res.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-10-23     Completed Date:  2002-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-84     Citation Subset:  IM    
Affiliation:
Division of Haematology, National Institute for Biological Standards and Control, South Mimms, Hertfordshire, UK. martin.ries@kinder.imed.uni-erlangen.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Carbohydrate Sequence
Enzyme Activation / drug effects
Fibrin / pharmacology
Fibrinogen / chemistry,  pharmacology*
Gas Chromatography-Mass Spectrometry
Humans
Infant, Newborn
Kinetics
Peptide Fragments / chemistry,  pharmacology
Plasminogen / metabolism*
Spectrometry, Mass, Fast Atom Bombardment
Tissue Plasminogen Activator / metabolism*
Chemical
Reg. No./Substance:
0/Peptide Fragments; 9001-31-4/Fibrin; 9001-32-5/Fibrinogen; 9001-91-6/Plasminogen; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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