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

Higuchi, Shigesada; Murayama, Nobuhiro; Saguchi, Ken-ichi; Ohi, Hiroshi; Fujita, Yoshiaki; Camargo, Antônio Carlos Martins de; Ogawa, Tomoya; Deshimaru, Masanobu; Ohno, Motonori

doi:10.1016/s0162-3109(99)00119-8

Cited by 70 publications

(63 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prototypical BPP precursor found here contains five BPPs (Lm-BPP 1-5) interspersed with spacers, plus the 22-amino-acidlong CNP at the C terminus, and was further studied by means of resequencing the cDNAs characterized from the venom and is described elsewhere (Soares et al 2005). The remarkable feature is that Lm-BPP 1 is unique because it was shown by matrix-assisted laser desorption ionization time-of-flight mass spectrometry to be processed at the N terminus, being three residues shorter than that expected from the cDNA, beginning with a Trp at the N terminus (Soares et al 2005), whereas all other purified BPPs have a N-terminal Gln residue that is circularized to pyroglutamate (Higuchi et al 1999).…”

Section: Resultsmentioning

confidence: 99%

Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

et al. 2006

View full text Add to dashboard Cite

Efforts to describe toxins from the two major families of venomous snakes (Viperidae and Elapidae) usually reveal proteins belonging to few structural types, particular of each family. Here we carried on an effort to determine uncommon cDNAs that represent possible new toxins from Lachesis muta (Viperidae). In addition to nine classes of typical toxins, atypical molecules never observed in the hundreds of Viperidae snakes studied so far are highly expressed: a diverging C-type lectin that is related to Viperidae toxins but appears to be independently originated; an ohanin-like toxin, which would be the third member of the most recently described class of Elapidae toxins, related to human butyrophilin and B30.2 proteins; and a 3FTx-like toxin, a new member of the widely studied three-finger family of proteins, which includes major Elapidae neurotoxins and CD59 antigen. The presence of these common and uncommon molecules suggests that the repertoire of toxins could be more conserved between families than has been considered, and their features indicate a dynamic process of venom evolution through molecular mechanisms, such as multiple recruitments of important scaffolds and domain exchange between paralogs, always keeping a minimalist nature in most toxin structures in opposition to their nontoxin counterparts.

show abstract

Section: Resultsmentioning

confidence: 99%

Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The presence of many natriuretic peptides has been reported in snake venom (27,28). A gene has been identified that codes for seven bradykinin-potentiating peptides and also a C type natriuretic peptide in the venom of Bothrops jararaca by Camargos group (29) and the diuretic and natriuretic effects promoted by the peptide called DNP, isolated from the serpent Dendroaspis angusticeps (green mamba), have been recently described (30).…”

Section: Discussionmentioning

confidence: 99%

Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat kidney

Monteiro

Silva

Martins

et al. 2001

Braz J Med Biol Res

View full text Add to dashboard Cite

Many studies have reported the occurrence of lethal acute renal failure after snakebites. The aim of the present investigation was to determine alterations in renal function produced by Crotalus durissus terrificus venom and crotoxin as well as the histological alterations induced by these venoms. Isolated kidneys from Wistar rats weighing 240 to 280 g were perfused with Krebs-Henseleit solution containing 6 g% of previously dialyzed bovine serum albumin. The effects of Crotalus durissus terrificus venom and crotoxin were studied on glomerular filtration rate (GFR), urinary flow (UF), perfusion pressure (PP) and percentage sodium tubular transport (%TNa + ). The infusion of Crotalus durissus terrificus venom (10 µg/ml) and crotoxin (10 µg/ml) increased GFR (control 80 = 0.78 ± 0.07, venom 80 = 1.1 ± 0.07, crotoxin 80 = 2.0 ± 0.05 ml g -1 min -1 , P<0.05) and UF (control 80 = 0.20 ± 0.02, venom 80 = 0.32 ± 0.03, crotoxin 80 = 0.70 ± 0.05 ml g -1 min -1 , P<0.05), and decreased %TNa + (control 100 = 75.0 ± 2.3, venom 100 = 62.9 ± 1.0, crotoxin 80 = 69.0 ± 1.0 ml g -1 min -1 , P<0.05). The infusion of crude venom tended to reduce PP, although the effect was not significant, whereas with crotoxin PP remained stable during the 100 min of perfusion. The kidneys perfused with crude venom and crotoxin showed abundant protein material in the urinary space and tubules. We conclude that Crotalus durissus terrificus venom and crotoxin, its major component, cause acute nephrotoxicity in the isolated rat kidney. The current experiments demonstrate a direct effect of venom and crotoxin on the perfused isolated kidney.

show abstract

“…itors of angiotensin-converting enzyme was developed based on bradykinin-potentiating peptides from South American snake venoms (15). Inhibitors of platelet aggregation, such as eptifibatide and tirofiban, were designed based on disintegrins, a large family of platelet aggregation inhibitors found in viperid and crotalid snake venoms (16 -21).…”

mentioning

confidence: 99%

Hemextin AB Complex, a Unique Anticoagulant Protein Complex from Hemachatus haemachatus (African Ringhals Cobra) Venom That Inhibits Clot Initiation and Factor VIIa Activity

Banerjee

Mizuguchi

Iwanaga

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

During injury or trauma, blood coagulation is initiated by the interaction of factor VIIa (FVIIa) in the blood with freshly exposed tissue factor (TF) to form the TF⅐FVIIa complex. However, unwanted clot formation can lead to death and debilitation due to vascular occlusion, and hence, anticoagulants are important for the treatment of thromboembolic disorders. Here, we report the isolation and characterization of two synergistically acting anticoagulant proteins, hemextins A and B, from the venom of Hemachatus haemachatus (African Ringhals cobra). N-terminal sequences and CD spectra of the native proteins indicate that these proteins belong to the three-finger toxin family. Hemextin A (but not hemextin B) exhibits mild anticoagulant activity. However, hemextin B forms a complex (hemextin AB complex) with hemextin A and synergistically enhances its anticoagulant potency. Prothrombin time assay showed that these two proteins form a 1:1 complex. Complex formation was supported by size-exclusion chromatography. Using a "dissection approach," we determined that hemextin A and the hemextin AB complex prolong clotting by inhibiting TF⅐FVIIa activity. The site of anticoagulant effects was supported by their inhibitory effect on the reconstituted TF⅐FVIIa complex. Furthermore, we demonstrated their specificity of inhibition by studying their effects on 12 serine proteases; the hemextin AB complex potently inhibited the amidolytic activity of FVIIa in the presence and absence of soluble TF. Kinetic studies showed that the hemextin AB complex is a noncompetitive inhibitor of soluble TF⅐FVIIa amidolytic activity, with a K i of 50 nM. Isothermal titration calorimetric studies showed that the hemextin AB complex binds directly to FVIIa with a binding constant of 1.62 ؋ 10 5 M ؊1 . The hemextin AB complex is the first reported natural inhibitor of FVIIa that does not require a scaffold to mediate its inhibitory activity. Molecular interactions of the hemextin AB complex with FVIIa/TF⅐FVIIa will provide a new paradigm in the search for anticoagulants that inhibit the initiation of blood coagulation.

show abstract

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

Cited by 70 publications

References 19 publications

Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

Lachesis muta (Viperidae) cDNAs Reveal Diverging Pit Viper Molecules and Scaffolds Typical of Cobra (Elapidae) Venoms: Implications for Snake Toxin Repertoire Evolution

Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat kidney

Hemextin AB Complex, a Unique Anticoagulant Protein Complex from Hemachatus haemachatus (African Ringhals Cobra) Venom That Inhibits Clot Initiation and Factor VIIa Activity

Contact Info

Product

Resources

About