Date of Graduation

Fall 2011

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Rehana Levely

Abstract

Fibrinogen gamma' (Y') is a minor isoform of fibrinogen, a plasma protein that contains an altered Y chain due to an insertion sequence of 20 amino acids. The fibrinogen Y' chain binds to thrombin with high affinity at a positively charged surface or exosite II, mainly through its interactions at residues 410-427. Several recent studies have shown that binding of fibrinogen Y' inhibits thrombin induced platelet aggregation and the presence of fibrinogen Y' changes clot architecture. Fibrinogen Y' peptide has been shown to affect thrombin interaction with platelet receptors, mainly binding of thrombin to GpIb-α, and it prevents thrombin cleavage of protease activated receptor PAR-1. This study investigated the inhibitory effect of fibrinogen Y' peptide on thrombin- induced dense granule release and intraplatelet calcium mobilization which indicates platelets activation. My study have shown that the fibrinogen Y' peptide inhibits thrombin- induced dense granule release and calcium mobilization in platelets. In summary, fibrinogen Y' peptide binds to thrombin and inhibits the platelet response to thrombin. Thus, this study may help in assessing the effects of fibrinogen Y' and indicate the potential of fibrinogen Y' as an antithrombotic therapeutic agent.

Keywords

fibrinogen γ', thrombin, platelet activation, platelet receptors, antithrombotic

Subject Categories

Medical Molecular Biology

Copyright

© Amruta Ashtekar

Campus Only

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