8s9e

Structural highlights

Function

VM2JA_BOTJA Binds alpha-5/beta-1 (ITGAV/ITGB1), alpha-V/beta-3 (ITGAV/ITGB3) and alpha-M/beta-2 (ITGAM/ITGB2) integrins. Is a potent inhibitor of platelet aggregation induced by ADP, collagen, and thrombin. Induces neutrophil chemotaxis and inhibits the chemotaxis of human neutrophils toward fMLP, IL-8, and jarastatin itself. Directly activates an integrin-coupled signaling and modulate the MAPK pathway in different ways, leading the neutrophils to express different functional response. Jarastatin-treated neutrophils accumulates F-actin at the plasmalemma. Induces PTK2/FAK1 and phosphoinositide 3-kinase (PI3K) activation. Induces Erk-2 translocation to nucleus and a delay of the spontaneous apoptosis of neutrophils. Increases the IL-8 mRNA levels in neutrophils. When injected simultaneously with melanoma cells in mice, jarastatin, flavoridin (FL) and kistrin (KR), significantly reduce tumor lung colonization. Jarastatin inhibits B16F10 cell growth in vitro. When it interacts with melanoma cells, it induces actin cytoskeleton rearrangement, increasing actin polymerization and PTK2/FAK1 phosphorylation. Interferes with NF-kappaB translocation in melanoma cells.^{[1] [2] [3]}

References

1. ↑ Coelho AL, de Freitas MS, Oliveira-Carvalho AL, Moura-Neto V, Zingali RB, Barja-Fidalgo C. Effects of jarastatin, a novel snake venom disintegrin, on neutrophil migration and actin cytoskeleton dynamics. Exp Cell Res. 1999 Sep 15;251(2):379-87. PMID:10471323 doi:10.1006/excr.1999.4583
2. ↑ Coelho AL, De Freitas MS, Mariano-Oliveira A, Rapozo DC, Pinto LF, Niewiarowski S, Zingali RB, Marcinkiewicz C, Barja-Fidalgo C. RGD signaling modulating the human neutrophils chemotaxis, apoptosis and IL-8 gene expression. Exp Cell Res. 2004 Jan 15;292(2):371-84. PMID:14697344 doi:10.1016/j.yexcr.2003.09.013
3. ↑ Oliva IB, Coelho RM, Barcellos GG, Saldanha-Gama R, Wermelinger LS, Marcinkiewicz C, Benedeta Zingali R, Barja-Fidalgo C. Effect of RGD-disintegrins on melanoma cell growth and metastasis: involvement of the actin cytoskeleton, FAK and c-Fos. Toxicon. 2007 Dec 15;50(8):1053-63. PMID:17854854 doi:10.1016/j.toxicon.2007.07.016