|Support type:||Scholarships in Brazil - Master|
|Effective date (Start):||March 01, 2010|
|Effective date (End):||February 29, 2012|
|Field of knowledge:||Biological Sciences - Biochemistry - Chemistry of Macromolecules|
|Principal Investigator:||Guacyara da Motta|
|Grantee:||Camila Lopes Veronez|
|Home Institution:||Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil|
Human plasma kallikrein-kinin system is formed by plasma kallikrein (huPK), which hydrolyzes its natural substrate high molecular weight kininogen (HK) and releases bradykinin (BK), and this system is related to vascular biology interacting with coagulation, fibrinolysis and complement systems.BK (RPPGFSPFR) can reproduce the characteristics of inflammatory state, such as the increase of vascular permeability, through the production of molecules such as messengers and effectors. This vasoactive peptide is also related to the increase of tumor progression through increase of vascular permeability.HK has both antithrombotic and profibrinolytic activities, controls local blood pressure through BK release and also has antiadhesive properties on cell interactions. The kininogen interaction with cell surface is important for accumulation of kinin precursors on cells. The kinin-free HK (HKa) inhibits angiogenesis and BK promotes angiogenesis.HuPK plays role in blood pressure through BK release from HK, activates factor XII to factor XIIa, participates in fibrinolysis and plays role in the alternative pathway of complement system. The immunolocalisation of either plasma prekallikein (PK) or plasma kallikrein (huPK) in the cytoplasm and on the nuclear envelope of a wide variety of cells suggests a physiological importance of this enzyme which should be studied more in details. Recent investigations have shown that the zymogen PK has enzymatic activity.We have shown in recent work that HK interaction with both endothelial cells and tumor cells results in its endocytosis involving heparan sulfate proteoglycan suggesting that it is a novel additional mechanism which may control kinin generation at the cell surface. The aim of this study is to investigate the interaction of human plasma prekallikrein with cell surface and its activity as zymogen.