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

Ries, M., Easton, R.L., Longstaff, C., Zenker, M., Corran, P.H., Morris, H.R., Dell, A. and Gaffney, P. (2001) 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. Thrombosis Research, 103 3: 173-184. doi:10.1016/S0049-3848(01)00289-4


Author Ries, M.
Easton, R.L.
Longstaff, C.
Zenker, M.
Corran, P.H.
Morris, H.R.
Dell, A.
Gaffney, P.
Title 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
Journal name Thrombosis Research   Check publisher's open access policy
ISSN 0049-3848
Publication date 2001-08-01
Sub-type Article (original research)
DOI 10.1016/S0049-3848(01)00289-4
Volume 103
Issue 3
Start page 173
End page 184
Total pages 12
Editor Birger Blomback
Colvin Redman
Place of publication Elmsford, N.Y. U.S.A.
Publisher Pergamon Press
Collection year 2001
Language eng
Subject C1
321008 Haematology
730199 Clinical health not specific to particular organs, diseases and conditions
Formatted abstract
Our study investigates the effect of fetal and adult soluble fibrin (SF), fetal and adult fibrinogen Aα- and γ-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 Bβ- and γ-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 kcat app than the respective adult types. No differences could be seen in the values for Km 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 Bβ- and γ-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.
Keyword Activation kinetics
Fibrin
Glycosylation
Plasminogen
Neonates
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 02:31:08 EST