Inhibitory effects of recombinant RTS-jerdostatin on integrin α1β1 function during adhesion, migration and proliferation of rat aortic smooth muscle cells and angiogenesis.

Jerdostatin, a short RTS-disintegrin cloned from venom gland mRNA of Protobothrops jerdonii, selectively blocks the adhesion of α1β1 integrin to collagen IV. Integrin α1β1 is highly expressed in smooth muscle cells (SMC) surrounding small blood vessels and vascular endothelial cells. Vascular SMC adhesion, migration and proliferation are important processes during normal vascular development.

Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins.

Significance: The extracellular matrix (ECM) fulfills essential functions in multicellular organisms. It provides the mechanical scaffold and environmental cues to cells. Upon cell attachment, the ECM signals into the cells.

Integrin α7β1 is a redox-regulated target of hydrogen peroxide in vascular smooth muscle cell adhesion.

Upon adhesion to laminin-111, aortic smooth muscle cells initially form membrane protrusions with an average diameter of 2.9μm. We identified these protrusions also as subcellular areas of increased redox potential and protein oxidation by detecting cysteine sulfenic acid groups with dimedone.

Recombinant expression in human cells of active integrin alpha 1 beta 1-blocking RTS-disintegrin jerdostatin.

Jerdostatin, an RTS short disintegrin cloned from Protobothrops jerdonii and recombinantly produced in Escherichia coli, is a potent and specific antagonist of the alpha(1)beta(1) integrin. Jerdostatin selectively blocked the adhesion of alpha(1)beta(1)-K562 cell to collagens I and IV in vitro and angiogenesis in vivo. Here we report the recombinant production of jerdostatin in a mammalian cell system, a prerequisite for developing a conditional transgenic mouse to investigate the effect of systemic expression of jerdostatin on tumor development.

Structure-function studies of Tityus serrulatus Hypotensin-I (TsHpt-I): A new agonist of B(2) kinin receptor.

In order to better understand the relationship between the primary structure of TsHpt-I - a bradykinin-potentiating peptide (BPP) isolated from the venom of the yellow scorpion Tityus serrulatus, with a non-canonical Lys residue prior to the conservative Pro-Pro doublet - and its cardiovascular effects, a series of ladder peptides were synthesized using the C-terminal portion of TsHpt-I as a template. All synthetic peptides having the Pro-Pro doublet at their C-terminal were able to potentiate the hypotensive effect of bradykinin. Conversely, only those analogues having Lys residue could induce a transient hypotension when intravenously administrated in male rats, indicating that the positive charge located toward the radical of this amino acid residue is crucial for this cardiovascular effect.