SLOVENSKO BIOKEMIJSKO DRUŠTVO vabi na 125. društveno predavanje z naslovom: A PROTEIN FROM PLANT SOURCE EcTI IS HIGHLY SELECTIVE FOR INHIBITION OF MAMMALIAN ENZYMES PLAYING A ROLE AS AN ANTI-INFLAMMATORY, ANTITHROMBOTIC, AND ANTI-TUMOR AGENT

SLOVENSKO BIOKEMIJSKO DRUŠTVO

vabi na 125. društveno predavanje.

Predavala bo

Prof. Dr. Maria Luiza Oliva

Departamento de Bioquímica, Universidade Federal de São Paulo,

São Paulo, Brazil

A PROTEIN FROM PLANT SOURCE EcTI IS HIGHLY SELECTIVE FOR INHIBITION OF MAMMALIAN ENZYMES PLAYING A ROLE AS AN ANTI-INFLAMMATORY, ANTITHROMBOTIC, AND ANTI-TUMOR AGENT

Predavanje bo v torek, 4. marca 2014, ob 13h

v predavalnici B3 na Biološkem središču, NIB

Večna pot 111, 1000 Ljubljana

POVZETEK PREDAVANJA

The high-resolution crystal structures of free EcTI, a Kunitz proteinase inhibitor, of its complex with bovine trypsin, was determined. The action of EcTI has been studied in inflammation, coagulation, and tumor models since, in addition to trypsin, EcTI also, by yet not qute revealed mechanism, inhibits plasmin, plasma kallikrein, human neutrophil elastase, and the activation of both MMP-2 and MMP-9.

EcTI inhibited the adhesion, migration, and cell invasion of gastric cancer cells by decreasing their expression and by disrupting the cellular organization of molecules involved in the formation and maturation of invadopodia, such as integrin β1, cortactin, neuronal Wiskott-Aldrich syndrome protein, membrane type 1 metalloproteinase, and MMP-2. Moreover, gastric cancer cells treated with EcTI exhibited significant decrease in intracellular phosphorylated Src and focal adhesion kinase, both integrin-dependent cell signaling components. In vivo, EcTI impaired the development of murine melanoma by decreasing the tumor volume 80-90%.

EcTI also showed anti-inflammatory activity since the extent of roller, adherence and migration of the cell behavior exacerbated in LPS-induced inflammatory response was reduced in the EcTI-treated group. Finally, as numerous studies have shown, the relationship between cancer and coagulopathy, the antithrombotic action of this protein, in a model of arterial thrombosis, was also investigated and the inhibitor was able to prolong the time to total occlusion of the carotid artery, indicating that this potent multifunctional plant inhibitor is also able to prevent thrombosis. Thus, EcTI may contribute to the elucidation of biochemical pathways involved in inflammation, tumor repression, and thrombosis, among other pathogenic conditions.

Gostiteljica je prof. dr. Tamara Lah Turnšek (direktorica NIB, Ljubljana).

Predavanje bo v angleškem jeziku.