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PubMed2003

Immunogenicity of venoms from four common snakes in the South of Vietnam and development of ELISA kit for venom detection.

The antigenicity and antigenic relationship between venoms of four common snakes in the South of Vietnam-Trimeresurus popeorum, Calloselasma rhodostoma, Naja naja and Ophiophagus hannah-were studied. Most of venom components expressed antigenicity and produced high titre antivenoms. The venoms share common components and antivenoms cross-reacted along them. Furthermore, cross-reactions were observed among non-common antigens, indicating that they share common epitopes. Hence, using single component as immunogen for species diagnosis of snakebites can reduce cross-reaction, perhaps may not be totally specific. A three-step affinity purification protocol was set up for preparation of species-specific antivenom antibodies. The steps involved affinity chromatography of IgG from hyper-immunized rabbit sera with protein A columns, immuno-affinity chromatography of monovalent antivenom antibodies with respective homologous venom columns, and immuno-absorption of cross-species reacting antibody molecules with heterologous venom columns. The antibodies were then used for construction of an enzyme-linked immunosorbent assay (ELISA) test kit. The kit can differentiate among the four common snake venoms in various types of samples with the detection limit of 0.2-1.6 ng/ml, depending on the type of samples and species of the snake. The efficacy of this kit for snake venom detection was successfully demonstrated in experimental envenomation in rats. Preliminary evaluation with 140 samples taken from 88 human snakebite victims in Vietnam showed that the kit could detect venom in human samples and would be a very useful tool for fast identification of snakebites in clinics.

Animals↗
PubMed2002

Toxicity of South American snake venoms measured by an in vitro cell culture assay.

Cytotoxicity of venoms from eight medically important South American Crotalidae snakes (Bothrops and Lachesis genera) was determined, based on a procedure originally described for the screening of cytotoxic agents in general. The assay, the conditions of which were adapted to snake venoms, determines the survival of viable cells in monolayer culture upon exposure to the toxic agent. Snake venom toxicity was expressed as the venom dose that killed 50% of the cells (CT(50)) under the assay conditions. Bothrops neuwieddi mattogrossensis (CT(50)=4.74+/-0.35 microg/ml) and Bothrops leucurus (CT(50)=4.95+/-0.51 microg/ml) were the most cytotoxic whereas Bothrops atrox (CT(50)=34.64+/-2.38 microg/ml) and Bothrops sp. (CT(50)=33.89+/-3.89 microg/ml) were the least cytotoxic venoms, respectively. The relationship between CT(50) and other biological activities of these snake venoms was evaluated.

Animals↗
PubMed2003

The efficacy of two antivenoms against the venom of North American snakes.

Mortality due to snake envenomation is not a major problem in the United States with approximately 8-12 deaths per year, but envenomation is a serious problem that can result in functional disability, loss of extremities, and a costly recovery. Physicians encounter different clinical situations with each new snakebite victim because of the geographical variations in snake venoms. The best and most acceptable form of treatment is the use of antivenom; however, it must be administered as soon as possible since it is not so effective at reducing local signs of envenomation such as necrosis. The antivenom in the United States is in short supply, expensive and may not even be the most effective for neutralizing all North American snake venoms. In this study, we tested two antivenoms. The first was a Crotalidae Polyvalent Fab fragment with Ovine origin (FabO) manufactured in London, and the second was Antivipmyn, a Mexican manufactured antivenom that is F(ab')(2) fragment produced in horse (Fab(2)H). The efficacy of the two antivenoms was tested with 15 different snake venoms found in North America. Three different assays were used to test the efficacy of the antivenoms, the in vivo serum protection test (ED(50)), antihemorrhagic and anticoagulant. The Fab(2)H antivenom was most effective in neutralizing the hemorrhagic activity of 78% of the hemorrhagic venoms used in this study. In the ED(50) assay, the Fab(2)H antivenom was effective in neutralizing all venoms used in this study, while FabO neutralized all but C. m. molossus venom. However, in most cases, FabO required less antivenom than Fab(2)H antivenom to neutralize three LD(50).

Animals↗
PubMed1999

Bradykinin-potentiating peptides and C-type natriuretic peptides from snake venom.

Cloning of cDNAs encoding bradykinin-potentiating peptides (BPPs)-C-type natriuretic peptide (CNP) precursor or its homologue was performed for cDNA libraries of Bothrops jararaca (South American snake), Trimeresurus flavoviridis, Trimeresurus gramineus and Agkistrodon halys blomhoffi (Asian snakes), all belonging to Crotalinae subfamily. Each cDNA library was constructed from the venom glands of a single snake to preclude ambiguity by intraspecies variation in venom components. Thirteen positive clones derived from B. jararaca were divided into two types depending on restriction sites. Differences in the nucleotide sequence arise at three locations and two of them accompanied amino acid conversions. Despite the differences, both types of cDNA clones encode the BPP-CNP precursor of 256 amino acid residues. Sequence analysis demonstrated that cDNA clones from three Asian snakes encode homologues of the BPP-CNP precursor from B. jararaca. In a precursor polypeptide, a signal sequence (approximately 25 aa) at the N-terminus is followed by sequences of BPP or the analogue (5-13 aa) with flanking spacer sequences (indefinite number of aa), an intervening linker sequence (approximately 144 aa) with unidentified function, and a CNP sequence (22 aa) with a preceding processing signal sequence (10 aa). cDNA clones from A. halys blomhoffi encode two distinct peptides in place of BPP, and T. flavoviridis and T. gramineus were shown to have considerably different sequences in the BPP domain from those known as BPP sequences. The present results provide evidence for a wide distribution of the orthologous gene expressing a series of bioactive peptides among Crotalinae subfamily.

3' Untranslated Regions↗
PubMed1997

Acetylcholinesterases from Elapidae snake venoms: biochemical, immunological and enzymatic characterization.

We analyzed 45 batches of venom from 20 different species belonging to 11 genera from the 3 main families of venomous snakes (Elapidae, Viperidae and Crotalidae). We found high acetylcholinesterase (AChE) activity in all venoms from Elapidae, except in those from the Dendroaspis genus. AChE was particularly abundant in Bungarus venoms which contain up to 8 mg of enzyme per gram of dried venom. We could not detect acetylcholinesterase activity in any batch of venom from Viperidae or Crotalidae. Titration of active sites with an organophosphorous agent (MPT) revealed that the AChE of all venoms have similar turnovers (6000 to 8000 s(-1)) which are clearly higher than those of Torpedo and mammalian enzymes but lower than that of Electrophorus. AChEs from the venom of elapid snakes of the Bungarus, Naja, Ophiophagus and Haemacatus genera were purified by affinity chromatography. SDS-PAGE analysis and sucrose gradient centrifugation demonstrated that AChE is exclusively present as a nonamphiphilic monomer. These enzymes are true AChEs, hydrolyzing acetylthiocholine faster than propionylthiocholine and butyrylthiocholine and exhibiting excess substrate inhibition. Twenty-seven different monoclonal antibodies directed against AChE from Bungarus fasciatus venom were raised in mice. Half of them recognized exclusively the Bungarus enzyme while the others cross-reacted with AChEs from other venoms. Polyspecific mAbs were used to demonstrate that venoms from Dendroaspis, which contain the AChE inhibitor fasciculin but lack AChE activity, were also devoid of immunoreactive AChE protein. AChE inhibitors acting at the active site (edrophonium, tacrine) and at the peripheral site (propidium, fasciculin), as well as bis-quaternary ligands (BW284C51, decamethonium), were tested against the venom AChEs from 11 different species. All enzymes had a very similar pattern of reactivity with regard to the different inhibitors, with the exception of fasciculin. AChEs from Naja and Haemacatus venoms were relatively insensitive to fasciculin inhibition (IC50 >> 10(-6) M), while Bungarus (IC50 approximately 10(-8) M) and especially Ophiophagus (IC50 < 10(-10) M) AChEs were inhibited very efficiently. Ophiophagus and Bungarus AChEs were also efficiently inhibited by a monoclonal antibody (Elec-410) previously described as a specific ligand for the Electrophorus electricus peripheral site. Taken together, these results show that the venoms of most Elapidae snakes contain large amounts of a highly active non-amphiphilic monomeric AChE. All snake venom AChEs show strong immunological similarities and possess very similar enzymatic properties. However, they present quite different sensitivity to peripheral site inhibitors, fasciculin and the monoclonal antibody Elec-410.

Acetylcholinesterase↗
PubMed2002

Cell-based dual snake model: a new approach to extracting highly winding boundaries in the ultrasound images.

Two common deficiencies of most conventional deformable models are the need to place the initial contour very close to the desired boundary and the incapability of capturing a highly winding boundary for sonographic boundary extraction. To remedy these two deficiencies, a new deformable model (namely, the cell-based dual snake model) is proposed in this paper. The basic idea is to apply the dual snake model in the cell-based deformation manner. While the dual snake model provides an effective mechanism allowing a distant initial contour, the cell-based deformation makes it possible to catch the winding characteristics of the desired boundary. The performance of the proposed cell-based dual snake model has been evaluated on synthetic images with simulated speckles and on the clinical ultrasound (US) images. The experimental results show that the mean distances from the derived to the desired boundary points are 0.9 +/- 0.42 pixels and 1.29 +/- 0.39 pixels for the synthetic and the clinical US images, respectively.

Algorithms↗
PubMed2002

Aerobic metabolism during predation by a boid snake.

We quantified the oxygen uptake rates (VO(2)) and time spent, during the constriction, inspection, and ingestion of prey of different relative sizes, by the prey-constricting boid snake Boa constrictor amarali. Time spent in prey constriction varied from 7.6 to 16.3 min, and VO(2) during prey constriction increased 6.8-fold above resting values. This was the most energy expensive predation phase but neither time spent nor metabolic rate during this phase were correlated with prey size. Similarly, prey size did not affect the VO(2) or duration of prey inspection. Prey ingestion time, on the other hand, increased linearly with prey size although VO(2) during this phase, which increased 4.9-fold above resting levels, was not affected by prey size. The increase in mechanical difficulty of ingesting larger prey, therefore, was associated with longer ingestion times rather than proportional increases in the level of metabolic effort. The data indicate that prey constriction and ingestion are largely sustained by glycolysis and the intervening phase of prey inspection may allow recovery between these two predatory phases with high metabolic demands. The total amount of energy spent by B. c. amarali to constrict, inspect, and ingest prey of sizes varying from 5 to 40% of snake body mass varied inversely from 0.21 to 0.11% of the energy assimilated from the prey, respectively. Thus, prey size was not limited by the energetic cost of predation. On the contrary, snakes feeding on larger prey were rewarded with larger energetic returns, in accordance with explanations of the evolution of snake feeding specializations.

Animals↗
PubMed1999

Respiratory consequences of feeding in the snake Python molorus.

Snakes can ingest large meals and exhibit marked increases in metabolic rate during digestion. Because postprandial oxygen consumption in some snakes may surpass that attained during exercise, studies of digestion offers an alternative avenue to understand the cardio-respiratory responses to elevated metabolic rate in reptiles. The effects of feeding on metabolic rate, arterial oxygen levels, and arterial acid-base status in the snake Python molorus are described. Four snakes (180-250 g) were cannulated in the dorsal aorta and blood samples were obtained during 72 h following ingestion of a meal (rat pups) exceeding 20% of body weight. Oxygen consumption increased from a fasting value of 1.71 +/- 0.08 to 5.54 +/- 0.42 ml kg-1 min-1 at 48 h following feeding, and the respiratory gas exchange ratio increased from 0.67 +/- 0.02 to a maximum of 0.92 +/- 0.03 at 32 h. Plasma lactate was always less than 0.5 mM, so the postprandial increase in metabolic rate was met by aerobic respiration. In fasting animals, arterial PO2 was 66 +/- 4 mmHg and haemoglobin-O2 saturation was 92 +/- 3%; similar values were recorded during digestion, but haematocrit decreased from 15.8 +/- 1.0 to 9.8 +/- 0.8 due to repeated blood sampling. Plasma [HCO3-] increased from a fasting level of 19.3 +/- 0.8 to 25.8 +/- 1.0 mmol l-1 at 24 h after feeding. However, because arterial PCO2 increased from 21.1 +/- 0.5 to 27.9 +/- 1.4 mmHg, there was no significant change in arterial pH from the fasting value of 7.52 +/- 0.01. Acid-base status returned to pre-feeding levels at 72 h following feeding. The increased arterial PCO2 is most likely explained by a reduction in ventilation relative to metabolism, but we predict that lung PO2 does not decrease below 115 mmHg. Although ingestion of large meals is associated with large metabolic changes in pythons, the attendant changes in blood gases are relatively small. In particular, the small changes in plasma [HCO3-] and stable pH show that pythons respond very differently to digestion than alligators where very large alkaline tides have been observed. It is unclear why pythons and alligators differ in the magnitude of their responses, but given these interspecific differences it seems worthwhile to describe arterial blood gases during digestion in other species of ectothermic vertebrates.

Acid-Base Imbalance↗
PubMed2003

Discriminant snakes for 3D reconstruction of anatomical organs.

In this work a new statistic deformable model for 3D segmentation of anatomical organs in medical images is proposed. A statistic discriminant snake performs a supervised learning of the object boundary in an image slice to segment the next slice of the image sequence. Each part of the object boundary is projected in a feature space generated by a bank of Gaussian filters. Then, clusters corresponding to different boundary pieces are constructed by means of linear discriminant analysis. Finally, a parametric classifier is generated from each contour in the image slice and embodied into the snake energy-minimization process to guide the snake deformation in the next image slice. The discriminant snake selects and classifies image features by the parametric classifier and deforms to minimize the dissimilarity between the learned and found image features. The new approach is of particular interest for segmenting 3D images with anisotropic spatial resolution, and for tracking temporal image sequences. In particular, several anatomical organs from different imaging modalities are segmented and the results compared to expert tracings.

Algorithms↗
PubMed2003

Molecular cloning and expression of a functional snake venom serine proteinase, with platelet aggregating activity, from the Cerastes cerastes viper.

The venoms of Viperidae snakes contain numerous serine proteinases that have been recognized to possess one or more of the essential activities of thrombin on fibrinogen and platelets. Among them, a platelet proaggregant protein, cerastocytin, has been isolated from the venom of the Tunisian viper Cerastes cerastes. Using the RACE-PCR technique, we isolated and identified the complete nucleotide sequence of a cDNA serine proteinase precursor. The recombinant protein was designated rCC-PPP (for C. cerastes platelet proaggregant protein), since its deduced amino acid sequence is more than 96% identical to the partial polypeptide sequences that have been determined for natural cerastocytin. The structure of the rCC-PPP cDNA is similar to that of snake venom serine proteinases. The expression of rCC-PPP in Escherichia coli system allowed, for the first time, the preparation and purification of an active protein from snake venom with platelet proaggregant and fibrinogenolytic activities. Purified rCC-PPP efficiently activates blood platelets at nanomolar (8 nM) concentrations, as do natural cerastocytin (5 nM) and thrombin (1 nM). It is able to clot purified fibrinogen and to hydrolyze alpha-chains. Thus, rCC-PPP could be therefore considered a cerastocytin isoform. By comparison with other snake venom serine proteinases, a Gly replaces the conserved Cys(42). This implies that rCC-PPP lacks the conserved Cys(42)-Cys(58) disulfide bridge. A structural analysis performed by molecular modeling indicated that the segment of residues Tyr(67)-Arg(80) of rCC-PPP corresponds to anion-binding exosite 1 of thrombin that is involved in its capacity to induce platelet aggregation. Furthermore, the surface of the rCC-PPP molecule is characterized by a hydrophobic pocket, comprising the 90 loop (Phe(90)-Val(99)), Tyr(172), and Trp(215) residues, which might be involved in the fibrinogen clotting activity of rCC-PPP.

Amino Acid Sequence↗
PubMed2002

Amino acid sequence of the alpha- and beta-globin chains of the Hiroo sea snake (Laticauda laticaudata).

We determined the hemoglobin complete amino acid sequences of the Hiroo sea snake (Laticaudia laticuada) from the intact globin chain, enzymatically digested fragments, and chemical cleavage fragments to analyze molecular evolution for classification of the sea snake. The Hiroo sea snake has two hemoglobin components, Hb-I and Hb-II, which contain different alpha- and beta-chains, respectively. This is the first report of the complete primary structure of a snake hemoglobin. The sequences were compared with those of other reptilian hemoglobins. Amino acid replacements at positions critical for structure and physiological role of hemoglobin were loosely conserved. The requirements for binding of ATP and of diphosphoglycerate as allosteric effectors at beta-globins seemed to be fullfilled.

Adenosine Triphosphate↗
PubMed1997

The role of nasal chemical senses in garter snake response to airborne odor cues from prey.

Garter snakes increase tongue-flick rates in the presence of airborne odorants (amyl acetate, limonene, earthworm wash vapor, fish water vapor, earthworms, goldfish) but not water vapor. Main olfactory (MO) nerve lesions result in loss of this tongue-flick rate elevation in the presence of airborne odorants. Vomeronasal (VN) nerve lesions result in a diminution of tongue-flick rate elevation. Garter snakes discriminate between the 2 arms of a maze containing airborne earthworm odor as compared with a blank control. Following MO nerve lesions, snakes fail to make this discrimination. Following VN nerve lesions or VN duct suture, snakes are initially able to make the discrimination but may eventually cease to prefer the prey-odor side of the maze and may stop eating prey rewards. These results support the idea that airborne odorants are detected by the main MO system and that such detection does not require a functional VN system.

Animals↗
PubMed2003

A prothrombin activator from Bothrops erythromelas (jararaca-da-seca) snake venom: characterization and molecular cloning.

A novel prothrombin activator enzyme, which we have named 'berythractivase', was isolated from Bothrops erythromelas (jararaca-da-seca) snake venom. Berythractivase was purified by a single cation-exchange-chromatography step on a Resource S (Amersham Biosciences) column. The overall purification (31-fold) indicates that berythractivase comprises about 5% of the crude venom. It is a single-chain protein with a molecular mass of 78 kDa. SDS/PAGE of prothrombin after activation by berythractivase showed fragment patterns similar to those generated by group A prothrombin activators, which convert prothrombin into meizothrombin, independent of the prothrombinase complex. Chelating agents, such as EDTA and o -phenanthroline, rapidly inhibited the enzymic activity of berythractivase, like a typical metalloproteinase. Human fibrinogen A alpha-chain was slowly digested only after longer incubation with berythractivase, and no effect on the beta- or gamma-chains was observed. Berythractivase was also capable of triggering endothelial proinflammatory and procoagulant cell responses. von Willebrand factor was released, and the surface expression of both intracellular adhesion molecule-1 and E-selectin was up-regulated by berythractivase in cultured human umbilical-vein endothelial cells. The complete berythractivase cDNA was cloned from a B. erythromelas venom-gland cDNA library. The cDNA sequence possesses 2330 bp and encodes a preproprotein with significant sequence similarity to many other mature metalloproteinases reported from snake venoms. Berythractivase contains metalloproteinase, desintegrin-like and cysteine-rich domains. However, berythractivase did not elicit any haemorrhagic response. These results show that, although the primary structure of berythractivase is related to that of snake-venom haemorrhagic metalloproteinases and functionally similar to group A prothrombin activators, it is a prothrombin activator devoid of haemorrhagic activity. This is a feature not observed for most of the snake venom metalloproteinases, including the group A prothrombin activators.

Amino Acid Sequence↗
PubMed1983

Neurotoxins from the venoms of the sea snakes Hydrophis ornatus and Hydrophis lapemoides.

The main neurotoxic components, toxins Hydrophis ornatus a and Hydrophis lapemoides a, were isolated from the venoms of the sea snakes Hydrophis ornatus and Hydrophis lapemoides respectively. The amino acid sequence of toxin Hydrophis ornatus a was deduced to be identical with that of toxin Astrotia stokesii a [Maeda & Tamiya (1978) Biochem. J. 175, 507-517] on the basis of identity of the tryptic peptide 'map' and the amino acid composition of each peptide. The amino acid sequence of toxin Hydrophis lapemoides a was determined mainly on the basis of identity of the amino acid compositions, mobilities on paper electrophoresis and migration positions on paper chromatography of the tryptic peptides with those of other sea-snake toxins whose sequences are known. Both toxins Hydrophis ornatus a and Hydrophis lapemoides a consisted of 60 amino acid residues and there were six amino acid replacements between them. The taxonomy of sea snakes in the Hydrophis ornatus complex has long been confused, and the above snakes were originally assigned to taxa that proved to be inconsistent with the relationships indicated by the neurotoxin amino acid sequences obtained. A subsequent re-examination of the specimens revealed an error in the original identifications and demonstrated the value of the protein amino acid sequences in systematic and phylogenetic studies. The isolation procedure and results of amino acid analysis of the tryptic peptides have been deposited as Supplementary Publication SUP 50121 (8 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained as indicated in Biochem. J. (1983) 209, 5.

Amino Acid Sequence↗
PubMed1985

Isolation and amino acid sequence of a short-chain neurotoxin from an Australian elapid snake, Pseudechis australis.

A short-chain neurotoxin Pseudechis australis a (toxin Pa a) was isolated from the venom of an Australian elapid snake Pseudechis australis (king brown snake) by sequential chromatography on CM-cellulose, Sephadex G-50 and CM-cellulose columns. Toxin Pa a has an LD50 (intravenous) value of 76 micrograms/kg body wt. in mice and consists of 62 amino acid residues. The amino acid sequence of Pa a shows considerable homology with those of short-chain neurotoxins of elapid snakes, especially of true sea snakes.

Amino Acid Sequence↗
PubMed1997

Biochemical characterization and pharmacological properties of a phospholipase A2 myotoxin inhibitor from the plasma of the snake Bothrops asper.

A protein that neutralizes the biological activities of basic phospholipase A2 (PLA2) myotoxin isoforms from the venom of the snake Bothrops asper was isolated from its blood by affinity chromatography with Sepharose-immobilized myotoxins. Biochemical characterization of this B. asper myotoxin inhibitor protein (BaMIP) indicated a subunit molecular mass of 23-25 kDa, an isoelectric point of 4, and glycosylation. Gel-filtration studies revealed a molecular mass of 120 kDa, suggesting that BaMIP possesses an oligomeric structure composed of five 23-25 kDa subunits. Functional studies indicated that BaMIP inhibits the PLA2 activity of B. asper basic myotoxins I and III, as well as the myotoxicity and edema-forming activity in vivo and cytolytic activity in vitro towards cultured endothelial cells, of all four myotoxin isoforms (I-IV) tested. Sequence analysis of the first 63 amino acid residues from the N-terminus of BaMIP indicated more than 65% sequence similarity to the PLA2 inhibitors isolated from the blood of the crotalid snakes Trimeresurus flavoviridis and Agkistrodon blomhoffii siniticus. These inhibitors also share sequences similar to the carbohydrate-recognition domains of human and rabbit cellular PLA2 receptors, suggesting a common domain evolution among snake plasma PLA2 inhibitors and mammalian PLA2 receptors. Despite this similarity, this is the first description of a natural anti-myotoxic factor from snake blood.

Amino Acid Sequence↗
PubMed2002

Cloning and characterization of novel snake venom proteins that block smooth muscle contraction.

In this study, we isolated a 25-kDa novel snake venom protein, designated ablomin, from the venom of the Japanese Mamushi snake (Agkistrodon blomhoffi). The amino-acid sequence of this protein was determined by peptide sequencing and cDNA cloning. The deduced sequence showed high similarity to helothermine from the Mexican beaded lizard (Heloderma horridum horridum), which blocks voltage-gated calcium and potassium channels, and ryanodine receptors. Ablomin blocked contraction of rat tail arterial smooth muscle elicited by high K+-induced depolarization in the 0.1-1 microm range, but did not block caffeine-stimulated contraction. Furthermore, we isolated three other proteins from snake venoms that are homologous to ablomin and cloned the corresponding cDNAs. Two of these homologous proteins, triflin and latisemin, also inhibited high K+-induced contraction of the artery. These results indicate that several snake venoms contain novel proteins with neurotoxin-like activity.

Agkistrodon↗
PubMed2004

A novel snake venom vascular endothelial growth factor (VEGF) predominantly induces vascular permeability through preferential signaling via VEGF receptor-1.

Vascular endothelial growth factor (VEGF)/vascular permeability factor induces both angiogenesis and vascular permeability mainly through VEGF receptor (VEGFR)-2 activation. VEGF binds VEGFR-1 as well, but the importance of VEGFR-1 signaling in vascular permeability has been largely neglected. Here, we report the purification and characterization of a novel VEGF-like protein from Trimeresurus flavoviridis Habu snake venom. The Habu snake has a venom-specific VEGF-like molecule, T. flavoviridis snake venom VEGF (TfsvVEGF), in addition to VEGF-A. TfsvVEGF has almost 10-fold less mitotic activity than VEGF(165), a predominant isoform of human VEGF-A, but a similar effect on vascular permeability. TfsvVEGF bound VEGFR-1 and induced its autophosphorylation to almost the same extent as VEGF(165), but bound VEGFR-2 weakly and induced its autophosphorylation almost 10-fold less effectively than VEGF(165). This unique binding affinity for VEGFR-1 and VEGFR-2 leads to the vascular permeability-dominant activity of TfsvVEGF. These results suggest that Habu snakes have acquired a highly purposive molecule for a toxin, which enhances the toxicity in envenomation without inducing effective angiogenesis and the following regeneration of damaged tissues, taking advantage of the difference in signaling properties involving VEGFR-1 and VEGFR-2 between vascular permeability and angiogenesis. TfsvVEGF is thus a potent inducing factor selective for vascular permeability through preferential signaling via VEGFR-1. These data strongly indicate the importance of VEGFR-1 signaling in vascular permeability.

Amino Acid Sequence↗