Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell.

Current therapies available for the treatment of human osteosarcoma, an aggressive bone tumor, are insufficient. To examine an alternative approach of integrin-based anti-osteosacoma strategy, acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin, was isolated and evaluated for its application in combination with two potent inhibitors of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8). The investigation of human osteosarcoma MG-63 cells pre-incubated with a FGF receptor-1 (FGFR-1) blocker AZD4547, a CXC-chemokine receptor-1/-2 (CXCR1/2) antagonist reparixin, and acurhagin-C via two given modes of separation and combination was executed.

Convulxin, a C-type lectin-like protein, inhibits HCASMCs functions via WAD-motif/integrin-αv interaction and NF-κB-independent gene suppression of GRO and IL-8.

Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs.

A critical role for the regulation of Syk from agglutination to aggregation in human platelets.

Agglucetin, a tetrameric glycoprotein (GP) Ibα agonist from Formosan Agkistrodon acutus venom, has been characterized as an agglutination inducer in human washed platelets (WPs). In platelet-rich plasma (PRP), agglucetin dramatically elicits a biphasic response of agglutination and subsequent aggregation. For clarifying the intracellular signaling events from agglutination to aggregation in human platelets, we examined the essential signaling molecules involved through the detection of protein tyrosine phosphorylation (PTP).

Atopic diathesis in patients with Kawasaki disease.

Objective: To determine the association between Kawasaki disease (KD) and atopic diathesis (atopic dermatitis [AD], allergic rhinitis, and asthma) in children younger than 5 years of age.

Study Design: In this nationwide study, we aimed to analyze the association and temporal relationship between KD and atopic diathesis. Data were obtained from the National Health Insurance Research Database of Taiwan from 1997 to 2010.

Inhibition of integrins αv/α5-dependent functions in melanoma cells by an ECD-disintegrin acurhagin-C.

Acurhagin-C, a Glu-Cys-Asp (ECD)-disintegrin from Agkistrodon acutus venom, has been reported as an endothelial apoptosis inducer, previously. Here we further evaluate its potential applications in cancer therapy. In vitro assays indicated that acurhagin-C not only may influence the cell viability at higher concentration, but also can potently and dose-dependently decrease cell proliferation in murine B16-F10 melanoma.

Acurhagin-C, an ECD disintegrin, inhibits integrin alphavbeta3-mediated human endothelial cell functions by inducing apoptosis via caspase-3 activation.

Background And Purpose: Acurhagin, a member of versatile metalloproteinase disintegrins from Agkistrodon acutus venom, has been identified as a platelet aggregation inhibitor, previously. Here, acurhagin-C, the C-terminal Glu-Cys-Asp (ECD)-containing fragment of acurhagin, was evaluated for its biological activities and potential applications in anti-angiogenic therapy.

Experimental Approach: Human umbilical vein endothelial cells (HUVECs) were treated with acurhagin-C to assay effects on viability, apoptosis, adhesion, migration, invasion, proliferation and angiogenesis.

Agglucetin, a tetrameric C-type lectin-like venom protein, regulates endothelial cell survival and promotes angiogenesis by activating integrin alphavbeta3 signaling.

Agglucetin, a platelet glycoprotein (GP)Ib binding protein from Formosan Agkistrodon acutus (A. acutus) venom, could sustain human umbilical vein endothelial cell (HUVEC) proliferation and HUVEC adhering to immobilized agglucetin showed extensive spreading, which was strongly abrogated by integrin antagonists 7E3 and triflavin. Flow cytometric analyses confirmed the expression of GPIb complex on HUVEC is absent and fluorescein isothiocyanate (FITC)-agglucetin binds to HUVEC in a dose-dependent and saturable manner.

Purification and functional characterization of AAV1, a novel P-III metalloproteinase, from Formosan Agkistrodon acutus venom.

AAV1, an alkaline glycoprotein (GP), was purified from Agkistrodon acutus venom by two chromatographic steps on successive DEAE-Sephadex A-50 and Superdex 75 FPLC columns. AAV1 on SDS-PAGE under non-reducing conditions migrated as a monomeric and a polymeric forms with apparent molecular mass of 57 and 180 kDa, respectively. Upon reduction, it appeared as a single broad band with a mass of 50.

Primary structure and antiplatelet mechanism of a snake venom metalloproteinase, acurhagin, from Agkistrodon acutus venom.

Acurhagin has been characterized as a P-III hemorrhagic metalloproteinase. We herein report the complete sequence of acurhagin by molecular cloning. Analysis of the cDNA-predicted amino acid sequence encoding acurhagin precursor revealed that this mosaic Asn-linked glycoprotein possesses a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domains (189/205/102/114 residues), with an overall 87% identity to that of jararhagin, an integrin alpha2beta1-cleaving metalloproteinase.

A novel P-I class metalloproteinase with broad substrate-cleaving activity, agkislysin, from Agkistrodon acutus venom.

The venom of Viperdae is a rich source of metalloproteinases, which have potential clinical applications for lowering plasma fibrinogen or dissolving thrombi. Recently, we purified a novel proteinase from Formosan Agkistrodon acutus venom using DEAE-Sephadex A-50 and Mono-Q HR 5/5 column chromatography. The purified getatinolytic component, agkislysin, is a 22kDa-monomeric protein without Asn-linked sugar.

A tetrameric glycoprotein Ib-binding protein, agglucetin, from Formosan pit viper: structure and interaction with human platelets.

Agglucetin, a tetrameric agglutination inducer from the Formosan pit viper, has been identified as a platelet membrane glycoprotein (GP) Ib agonist and directly agglutinated fixed-platelets in the absence of von Willebrand factor (vWf). Here, we resolved the complete cDNA sequences of agglucetin subunits (alpha(1), alpha(2), beta(1) and beta(2)) by molecular cloning. Each cloned cDNA encoding the leader peptide (23 residues) and the mature subunit (131/135/123/126 residues) shares a high degree of homology to each other and the C-type lectin-like GP Ib-binding proteins (BPs).

Purification and characterization of a novel metalloproteinase, acurhagin, from Agkistrodon acutus venom.

Acurhagin, a high-molecular mass hemorrhagic metalloproteinase, was purified from the crude venom of Agkistrodon acutus using anion-exchange and hydrophobic interaction chromatography. Acurhagin is a monomer with a molecular mass of 51.4 kDa under non-reducing conditions on SDS-PAGE and 48,133 Da by mass spectrometry.