SEARCH · PubMed Health

Results for “Tityus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Proteomic characterization of Tityus championi venom and recombinant expression of its major neurotoxin.

BACKGROUND: Tityus championi is a species endemic to the southern Talamanca Mountain Range, along the border region between Costa Rica and Panama, and has been associated with severe clinical cases. Despite its medical relevance, the composition of its venom remains poorly studied. The present study aimed to characterize the proteomic composition of T. championi venom, identify its main toxin families, and recombinantly produce one of its most abundant and lethal toxins for potential use in antivenom development. METHODS: Venom composition was analyzed by tandem mass spectrometry (MS/MS), enabling the identification of venom proteins. Subsequently, one of its primary lethal toxins (Tcham27) was identified and recombinantly expressed. RESULTS: Proteomic analysis revealed that the most abundant family in the venom corresponded to metalloproteases, with 43 protein groups (17% of the total identifications), which are associated with processes such as hemorrhage, edema, inflammation, hypotension, and necrosis. CIIMET family toxins comprised 27 protein groups (11%). Among ion channel-acting toxins, 18 protein groups (7%) corresponded to sodium channel toxins and 14 (6%) to potassium channel toxins, homologous to components from geographically proximate species such as Tityus discrepans, Tityus cf. asthenes, and Tityus jaimei. Other relevant families included cysteine-rich secretory proteins (CRISPs; 6 proteins, 3%), serine proteases (5 proteins, 2%), and lectins (5 proteins, 2%). In addition, low-abundance components such as insulin-like growth factors, nucleotide pyrophosphatases, hyaluronidase, α-amylase, lipolysis-activated toxins, and chitinase were detected, contributing to the functional diversity of the venom. CONCLUSIONS: Proteomic characterization of T. championi venom demonstrates that metalloproteases constitute a major protein family alongside neurotoxins. Recombinant production of its most abundant toxic peptide, which is identical to toxins in the venom of geographically proximate Tityus species, provides a key tool for developing specific antivenoms.

Protein↗

PubMed1992

The beta-type toxin Ts II from the scorpion Tityus serrulatus: amino acid sequence determination and assessment of biological and antigenic properties.

The toxin Ts II from the venom of the Brazilian scorpion Tityus serrulatus was purified in two successive chromatographic steps. The amino acid sequence was then determined by automated Edman degradation of the reduced and S-carboxymethylated protein and of proteolytic peptides derived from it. This sequence appears to differ from that of previously characterized toxins found in this venom. However, it is identical to the recently published sequence of protein III-8 from the same venom [Possani et al., J Biol Chem 266:3178-3185, 1991], except that the C-terminus was found to be amidated. Homologies were found between the sequence of Ts II and that of other toxins from Tityus; in particular, the amino acid sequence of Ts II displays 72% sequence identity with Ts VII (also called Titx gamma). Consistent with this structural similarity, some biological properties of Ts II were found to be similar to those of Ts VII: Ts II has an intracerebroventricular LD50 of 6 ng, as compared to 0.6 ng for Ts VII; in a receptor binding assay Ts II, like Ts VII, was found to behave as a beta-type toxin and to inhibit the binding of the reference labelled toxin with a K0.5 of 5 x 10(-9) M, as compared to 7 x 10(-11) M for Ts VII. Nevertheless, Ts II is unable to bind to anti-Ts VII antibodies in radioimmunoassay experiments, indicating the non-conservation between the two toxins of at least some antigenically important residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1989

A simplified procedure for the fractionation of Tityus serrulatus venom: isolation and partial characterization of TsTX-IV, a new neurotoxin.

Five toxins from the venom of the Brazilian scorpion Tityus serrulatus were purified to homogeneity by a combination of ion exchange chromatography with ammonium bicarbonate buffer (pH 7.8) on CM-cellulose-52 and rechromatography on the same resin equilibrated with ammonium acetate buffer (pH 4.7). Four of these proteins, obtained in one or two steps in high yield and lethality (named toxins IX3, IX5, and X4 and XIII) were shown to be identical with other toxins already described. A fifth one, TsTX-IV, is reported as a new toxin. Except for IX3, which showed Gly as the sole N-terminal residue, the other four toxins showed Lys. TsTX-IV has an approximate mol. wt of 6880, an i.v. LD50, in mice, of 826 +/- 156 micrograms/kg and an intracisternal LD50 of 11 +/- 9 micrograms/kg, compared to 375 +/- 45 and 4.9 +/- 0.8, respectively, for the whole venom extract. It has 61 amino acid residues and an amino acid composition different from that of any other toxin from Tityus serrulatus venom so far described. Toxins IX5, TsTX-IV and XIII induced a prejunctional type of supersensitivity on the guinea pig vas deferens, probably due to an increased release of noradrenaline.

Amino Acids↗

PubMed1991

Acute gastric mucosal injury induced by toxins from Tityus serrulatus scorpion venom: a novel experimental model in the rat.

The effect of a partially purified fraction (T1) and toxin gamma purified from Tityus serrulatus scorpion venom, on gastric mucosa were investigated in anesthetized rats. The animals were injected i.v. with the T1 fraction (37.5 micrograms/100 g) or with saline and 60 min later were sacrificed and the stomachs resected. The gastric juice was measured and stereoscopic examination of the stomachs made. In animals injected with the T1 fraction there was an increase in volume, acidity and pepsin output of rat stomach. The T1 fraction also induced acute gastric injuries in the glandular mucosa, consisting of circular or linear ulcers, and punctiform lesions. Intravenous injection of 20 micrograms/100 g of a pure toxin obtained from Tityus serrulatus scorpion venom (toxin gamma) also induced similar lesions in the rat stomach. Our data indicate that the injection of T1 fraction or toxin gamma are good models to induce acute gastric ulcers in a short period of time in anesthetized rats.

Animals↗

PubMed1987

A study of myonecrosis induced by the venom of the scorpion tityus serrulatus.

The pathogenesis of skeletal muscle necrosis produced by Tityus Serrulatus venom was studied by means of light microscopy and electron microscopy. Wistar rats were inoculated subcutaneously, at some distance from the muscles under study, with a sublethal dose of scorpion venom. Samples were taken of the tibialis anterior muscles of both rear legs, 2, 7 and 24 hours postinoculation. Light microscopy analysis after 2 hours revealed certain changes identified as "delta lesions", and also the presence of hyperconcentrated muscle cells. Electron microscopy confirmed these lesions and also enabled us to identify a degree of discontinuity in the plasma membrane with a persistence of the basal membrane. Hyperconcentrated fibers could still be observed 7 hours postinoculation. Histochemical analysis revealed high levels of calcium within the fibers. 24 hours after inoculation with the venom, numerous phagocytic cells were found in the degenerated fibers. Muscle cells were also found to have undergone alterations indicative of an ischemic process. The most characteristic finding 7 days postinoculation was the appearance of regenerative fibers. After thirty days the muscles regained their normal appearance. It is suggested that Tityus Serrulatus venom induces myonecrosis by means of a twofold action: direct action, which gives rise in the first place to a rupture of the plasma membrane, permitting a massive entry of calcium this being a key factor in the process of cell lesion and an assumed indirect action due to ischemia.

Animals↗

PubMed1992

Isolation of a bradykinin-potentiating factor from scorpion Tityus serrulatus venom.

A bradykinin-potentiating factor was isolated and characterized from the scorpion Tityus serrulatus venom by chromatographic techniques and reverse phase followed by biological assays. This factor showed to be able to potentiate the contractile activity of the isolated guinea-pig ileum, inhibited the angiotensin-converting enzyme and potentiated the bradykinin-induced lowering of the arterial blood pressure in the rat.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1975

Prejunctional effects of a purified toxin from the scorpion Tityus serrulatus: release of 3H-noradrenaline and enhancement of transmitter overflow elicited by nerve stimulation.

The effects of a purified fraction of the venom of the Brazilian scorpion, Tityus serrulatus, were studied in isolated guinea-pig atria previously labelled with 3H-noradrenaline. Exposure to 0.3 and 1.0 mug/ml of the scorpion toxin resulted in a long lasting positive chronotropic effect which was concentration-dependent. The increase in atrial rate coincided with an enhancement in spontaneous outflow of radioactivity. The increase in outflow of radioactive products elicited by exposure to 1.0 mug/ml of the scorpion toxin was approximately 3-fold. 3H-noradrenaline accounted for 60% of the total increase in outflow of radioactivity elicited by the scorpion toxin and the 3H-deaminated glycol (3,4-dihydroxyphenyl-glycol) represented the main metabolite formed, accounting for approximately 35% of the total release. 20 min after exposure to 1.0 mug/ml of the scorpion toxin the overflow of the labelled transmitter elicited by accelerans nerve stimulation (4 Hz, during 60 sec. supramaximal voltage) was increased 8-fold. This effect of the scorpion toxin appears to be unrelated to inhibition of neuronal uptake, block of alpha-adrenoceptors or stimulation of beta-adrenoceptors. Consequently, in addition to releasing noradrenaline, the scorpion toxin enhances transmitter overflow elicited by nerve stimulation through a prejunctional effect which appears to reflect a nove mechanism of action.

Animals↗

PubMed1986

Toxin gamma of the scorpion Tityus serrulatus modifies both activation and inactivation of sodium permeability of nerve membrane.

The effects of the major neurotoxic fraction isolated from scorpion venom of Tityus serrulatus, TiTx gamma, on peripheral nerve membrane of Xenopus laevis were studied under current- and voltage-clamp conditions. 700 nmol/l TiTx gamma depolarized the membrane and induced spontaneous activity (150 s-1, maximum value), which ceased within a few minutes. It reduced the amplitude of the action potentials from 109 mV to 52 mV and increased their duration from 1.25 ms to 4.5 ms. 440 nmol/l TiTx gamma induced inward Na current flow at resting potential. The descending branch of the Na current-voltage curve was flattened and shifted approximately 10 mV to more negative potentials. Maximum Na permeability was reduced to about 20%. Both development of and recovery from inactivation of Na permeability were slowed. The steepness of the steady-state inactivation curve was decreased, but the mid-potential changed only insignificantly. No prepulse was necessary to elicit either a shift of activation or an inward current at resting potential. Expressing the toxin effect either in terms of the decrease of Na peak current or of the slowing of inactivation, half-maximum effects were found with 0.3 +/- 0.1 and 3.7 +/- 0.7 mumol/l TiTx gamma, respectively.

Action Potentials↗

PubMed1990

The complete amino acid sequence of toxin TsTX-VI isolated from the venom of the scorpion Tityus serrulatus.

The complete sequence of the toxin TsTX-VI from the venom of the scorpion Tityus serrulatus Lutz and Mello is presented. The sequence has been determined by automated Edman analysis of the reduced and carboxymethylated protein as well as of the resulting peptides, obtained from S. aureus protease and tryptic digestions. TsTX-VI is composed of 62 residues and has a calculated molecular weight of 6717. Homology studies with other scorpion toxins show that TsTX-VI is more similar to the Old World than to the North American scorpion toxins. The hydropathic index indicates that TsTX-VI is more hydrophobic than Ts-gamma. Toxicity studies carried out in mice demonstrate that i.v. injection of TsTX-VI is unable to evoke the usual symptoms induced by the typical neurotoxins of this venom, but only a generalized allergic reaction. These properties are important in clarifying the relationship between primary structure and biological function of scorpion toxins.

Amino Acid Sequence↗

PubMed1992

Molecular cloning and nucleotide sequence analysis of a cDNA encoding the main beta-neurotoxin from the venom of the South American scorpion Tityus serrulatus.

A cDNA encoding the main Tityus serrulatus beta-neurotoxin was isolated from a venom gland cDNA library by using an oligonucleotide probe. The amino acid sequence deduced from the cDNA nucleotide sequence indicated that the toxin is the processed product of a precursor containing: (i) a signal peptide of 20 residues; (ii) the amino acid sequence of the mature toxin; and (iii) an extra Gly-Lys-Lys tail at the C-terminal end before the termination codon. Thus, in addition to the removal of the signal peptide by a signal peptidase, the generation of the mature toxin requires both a post-translational cleavage by a carboxypeptidase specific for basic residues and the action of an alpha-amidating enzyme. These results also show that the biosynthetic pathway for beta-toxins of 'New World' scorpion venoms is similar to that already described for alpha-toxins of 'Old World' scorpion venoms.

Amino Acid Sequence↗

PubMed1990

Isolation and characterization of toxic proteins from the venom of the Venezuelan scorpion Tityus discrepans (Karsch).

Four toxic, electrophoretically homogeneous proteins were isolated by ion-exchange chromatography on CM-cellulose-52 from the venom of the scorpion Tityus discrepans (range North Central Venezuela), named TdIV, TdV, TdVIII and TdIX. Component TdVIII, with 56 amino acid residues and mol. wt 6140 was the most toxic by i.p. injections into mice and had an intracisternal LD50 of 7.9 micrograms protein/kg body weight. Amino acid compositions of components TdIV and TdV were very similar, suggesting that they could be highly homologous proteins, although presumably contaminated one by the other. A fifth component, named TdIII, non-toxic by i.p. injections, was also isolated in homogeneous form. The i.v. and intracisternal LD50 values of the whole T. discrepans venom were 2.5 mg/kg and 16.0 micrograms/kg, respectively.

Amino Acids↗

PubMed1991

Further characterization of toxins T1IV (TsTX-III) and T2IV from Tityus serrulatus scorpion venom.

Toxins T1IV (TsTX-III) and T2IV have been purified to homogeneity from Tityus serrulatus scorpion venom and further characterized. Their amino acid composition and SDS-PAGE reveal an approximate mol. wt of 7000. Their intracisternal LD50 (micrograms/kg) in mice were 12.9 +/- 1.6 and 3.0 +/- 0.5, while their N-terminal amino acid sequences were K-E-G-Y-A-M-D-H-E-G-C-K-F-S- and K-E-G-Y-L-M-D-H-E-G-C-K-L-S-C-F-I-R-P-S-G-Y-C-G-R-E-, respectively. This sequence of T2IV, its amino acid composition and its chromatographic and electrophoretic behaviour identify it as toxin gamma (TsTX-I), which is the major toxin from this venom. TsTX-III (13 to 102 micrograms/kg) produced a long lasting enhancement of the hypertensive effect of noradrenaline and a slight decrease of the hypotensive effect of acetylcholine, while T2IV (115 micrograms/kg) induced a prolonged hypotensive effect on the anesthetized rat. On the isolated guinea-pig vas deferens, TsTX-III (2.1 and 3.0 micrograms/ml) produced a horizontal shift of the dose-response curve for noradrenaline to the left with no change of the maximal response. At a concentration of 1.43 microM, it induced a prolongation of the duration of the B component of the compound action potential. This prolongation was strongly reduced after addition of tetrodotoxin.

Acetylcholine↗

PubMed1992

Purification of the main beta-toxin from Tityus serrulatus scorpion venom using high-performance liquid chromatography.

The venom of the Brazilian scorpion Tityus serrulatus was fractionated using high-performance liquid chromatography which allowed us to purify in two steps the main beta-type toxin of the venom. The toxin constituted about 15% of the absorbance at 280 nm and 50% of the toxicity of the venom. According to its amino acid content, its electrophoretic migration on Phast-Gel homogenous 20 and its biological properties both in vivo by intracerebroventricular injection to the mouse (LD50 = 30 ng/kg mouse) and in vitro by competition receptor assay on rat brain synaptosomes (K0.5 = 80 pM), the toxin was identified as toxin Ts VII already purified from the same venom using low-pressure liquid chromatography (BECHIS et al., 1984 Biochem. biophys. Res. Commun. 122, 1146). The high-performance liquid chromatographic technique used improved by a factor of four the amount of toxin purified.

Animals↗

PubMed1992

Effects of toxin Ts-gamma, purified from Tityus serrulatus scorpion venom, on the isolated rat atria.

By using a pair of silver/silver-chloride electrodes it was possible to record, simultaneously, the atrial electrogram and the atrial contractile force of rat atria, in an organ bath, containing Krebs-Ringer solution (30 degrees C, pH 7.4, bubbled with 95% O2 and 5% CO2). Addition of toxin Ts-gamma, purified from Tityus serrulatus scorpion venom, into the bath (1 microgram/ml), evoked complex effects characterized by an initial reduction of both rate and contractile force, followed by increase of force and reduction of rate and finally by reduction of both rate and force. The increase of contractile force was prevented by metoprolol and is, therefore, adrenergic in nature. The reduction of rate was concomitant with changes in the atrial electrogram in which a positive P wave was replaced by a diphasic P wave, while the positive Ta wave was depressed. Experiments with tetrodotoxin, atropine and physostigmine indicate that these effects are due to the release of acetylcholine from vagal endings.

Acetylcholine↗

PubMed1989

Effects of the venom of the Brazilian scorpion Tityus serrulatus and two of its fractions on the isolated diaphragm of the rat.

1. The effects of Tityus serrulatus venom and of two of its toxic fractions, toxin gamma (Tx gamma) and T2III1, on the rat isolated diaphragm were examined. 2. The crude venom (5 ng) facilitated the neuromuscular transmission and increased the twitch tension evoked by retrograde injection of Ach. 3. Tx gamma (25-100 ng) and fraction T2III1 (2.5 ng) also facilitated the neuromuscular transmission but only fraction T2III1 increased the twitch tension evoked by retrograde injection of Ach. 4. Tx gamma (50 ng) and fraction T2III1 (2.5 ng) produced a tetrodotoxin-sensitive increase in the frequency of miniature endplate potentials (m.e.p.p.) and a transitory reduction of the resting potential. The latter effect of the fractions was prevented by treating muscles with tetrodotoxin or D-tubocurarine. Fraction T2III1 also produced a tetrodotoxin-resistance increase of m.e.p.p. amplitude. 5. These results suggest that Tx gamma enhances Ach output through the activation of Na+ channels in the motor nerve terminals. Fraction T2III1 produced effects similar to those induced by Tx gamma but also acted at postjunctional sites, probably by increasing subsynaptic membrane sensitivity to the neurotransmitter.

Animals↗

PubMed1991

Effects of Tityus serrulatus scorpion venom and one of its purified toxins (toxin gamma) on the isolated guinea-pig heart.

1. The effects of Tityus serrulatus scorpion venom and its most important toxin (toxin gamma) were investigated on isolated guinea-pig hearts, perfused with Locke solution, by the Langendorff's method. 2. The cardiac contraction, the coronary flow and the electrocardiogram (ECG) were simultaneously recorded. 3. Bolus injections of 25, 50 or 100 micrograms of scorpion venom and 2.5, 5 or 10 micrograms of toxin gamma in the heart evoked complex effects which were divided into 3 phases: an initial phase (tachycardia or bradycardia associated with an increase in contractile force), an intermediate phase (oscillations of cardiac rate, contractile force and coronary flow, due to wandering pacemakers) and a third phase (sinus tachycardia). 4. The bradycardia and the oscillations of rhythm were prevented by atropine, whereas the tachycardia and the increase in contractile force were prevented either by reserpine or propranolol. 5. Scorpion venom or toxin gamma induced a ST segment displacement in the ECG, explained by a transitory myocardial hypoxia, due to an increase in the contractile force and a simultaneous decrease of the coronary flow. 6. Perfusion of the heart with Locke solution containing 2% scorpion antivenom prevented almost totally the effects elicited by the venom. 7. It is concluded that the complex effects induced by scorpion venom and toxin gamma are due to the simultaneous release of acetylcholine and catecholamines from postganglionic nerve fibers in the heart.

Animals↗

PubMed1986

Tityus serrulatus toxin VII bears pharmacological properties of both beta-toxin and insect toxin from scorpion venoms.

Some beta-toxins from the South American scorpion Tityus serrulatus (e.g. Ts VII) are highly toxic both for mouse and fly larva. Radioiodinated Ts VII and the insect toxin from the North African scorpion Androctonus australis Hector (AaH IT) bind to the same site on a house fly head synaptosomal fraction. These results reinforce the hypothesis about the existence of a correlated series of scorpion toxins as previously defined by amino acid compositions and sequences, and immunological and circular dichroism studies, in suggesting that Ts VII constitutes a link which may fill the pharmacological gap existing between beta-toxins and insect toxins such as AaH IT.

Animals↗

PubMed1989

Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus.

The effects of TsIV-5, a toxin isolated from the Brazilian scorpion Tityus serrulatus, on whole-cell and single-channel Na currents were determined in N18 neuroblastoma cells. In whole-cell records at a test potential of -10 mV, external application of 500 nM TsIV-5 slowed inactivation 20-fold and increased peak current by about one-third without changing time-to-peak. Both the steady-state activation and inactivation curves were shifted to more negative potentials. Other alpha scorpion toxins produce similar effects but the single-channel mechanism is not known. TsIV-5 caused a voltage-dependent prolongation of mean single-channel open time such that at a test potential of -60 mV no change was observed, whereas at -20 mV mean open time increased about threefold and prolonged bursting was observed. Macroscopic current reconstructed from summed single-channel records showed a characteristic toxin-induced potentiation of peak current and a 20-fold slowing of the decay phase. TsIV-5 does not discriminate between tissue-specific Na channel subtypes. Prolonged open times and bursting were also observed in toxin-treated Na channels from rat ventricular myocytes, rat cortical neurons, and mouse skeletal muscle. The toxin effects are shown to be consistent with a kinetic model in which TsIV-5 selectively interferes with the ability of the channel to reach the inactivated state.

Animals↗