The ability of venom-derived peptides to disrupt physiological processes in mammals provides an e... more The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy—kainic acid and pentylenetetrazole-induced model of seizures—and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpi...
<p>Figure shows a sequence alignment of the domain II paddle motif as found in 8 mammalian ... more <p>Figure shows a sequence alignment of the domain II paddle motif as found in 8 mammalian Na<sub>v</sub> channel isoforms. As a reference, the number in italic indicates the coordinates of the first Gly residue in hNa<sub>v</sub>1.1. Although the Ile in hNa<sub>v</sub>1.3 (position 830 according to hNa<sub>v</sub>1.3 coordinates, 840 according to hNa<sub>v</sub>1.1 coordinates) differs from the Phe found in other neuronal isoforms, this residue is not present within the paddle motif and may not be accessible to Tf2. The Ser at position 842 (hNa<sub>v</sub>1.3 coordinates—indicated in red) is unique among hNa<sub>v</sub>1.1–1.3.</p
<p>(A) The nucleotide sequence of Tf2 was obtained by HiSeq (Illumina, USA). Signal peptide... more <p>(A) The nucleotide sequence of Tf2 was obtained by HiSeq (Illumina, USA). Signal peptide is underlined, mature peptide is highlighted in gray, and the amidation set point is marked in italic. (B) Multiple sequence alignment of Tf2 with other Na<sub>v</sub> channel toxins. Toxins are presented by their short names and UniProt KB codes. Capital letters denote amino acids. Lower-case letters denote: h, hydrophobic; s, small; b, big; p, polar; t, tiny; a, aromatic; l, aliphatic. Positive (+) and negative (-) amino acid residues that are part of the consensus sequence are also colored. Cys residues are shaded in black. aa means amino acid residues, and %Id is the percentage of sequence identity with Tf2.</p
<p>(A) Structural alignment between Tf2 (in blue) and five other Na<sub>v</sub>... more <p>(A) Structural alignment between Tf2 (in blue) and five other Na<sub>v</sub> channel scorpion toxins—Ts1, Ts2, CssII, CssIV, and AaHII (in gray). (B) Comparison of electrostatic potentials between the toxins Tf2, Ts1, Ts2, CssII, CssIV, and AaHII. The figure shows charge distribution along the toxin surface, divided into faces A and B. Shown in red are acidic residues whereas blue represents basic residues; in white, neutral regions are shown.</p
Biochimica et Biophysica Acta (BBA) - General Subjects, 2014
The venoms of several scorpion species have long been associated with pancreatitis in animal mode... more The venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. The cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. Antarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, sharing relevant structural elements with previously reported metalloproteases of the ADAM family. The phylogenetic analysis reveals that the reported sequences cluster in groups that correlate with the geographical localization of the respective species. Antareases are ubiquitous to a broad range of scorpion species, where they could be catalytically active enzymes. These molecules can be used to describe the evolution of scorpion venoms under different ecogeographic constrains. For the first time the complete sequence of the antareases is reported. It is demonstrated that antareases are common in the venom of different scorpion species. They are now proposed as targets for antivenom therapies.
Dissertação(mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, 2010. A peçonha... more Dissertação(mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, 2010. A peçonha de aranhas tem provado ser uma fonte valiosa de componentes farmacologicamente ativos capazes de exercer as mais diversas funções. Por atuarem em diferentes sistemas biológicos, a caracterização de componentes bioativos desperta grande interesse na prospecção de novos fármacos. Poucos trabalhos com aranhas caranguejeiras brasileiras têm sido desenvolvidos nessa área e nenhum até o momento foi realizado com a peçonha de Nhandu coloratovillosus. O presente trabalho teve como objetivo caracterizar a composição bioquímica da peçonha de N. coloratovillosus visando à identificação de compostos bioativos. A peçonha bruta foi submetida a fracionamento por RP-HPLC e 35 frações foram eluídas. Análises por MALDI-TOF MS detectaram a presença de 46 componentes de massas moleculares distintas. Por meio de eletroforese foi possível visualizar a presença de componentes de alta massa molecular. Um compo...
Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater ... more Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by Pimelodus maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 μg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 μg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus.
The venoms of several scorpion species have long been associated with pancreatitis in animal mode... more The venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. The cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. Antarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, s...
The ability of venom-derived peptides to disrupt physiological processes in mammals provides an e... more The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy—kainic acid and pentylenetetrazole-induced model of seizures—and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpi...
<p>Figure shows a sequence alignment of the domain II paddle motif as found in 8 mammalian ... more <p>Figure shows a sequence alignment of the domain II paddle motif as found in 8 mammalian Na<sub>v</sub> channel isoforms. As a reference, the number in italic indicates the coordinates of the first Gly residue in hNa<sub>v</sub>1.1. Although the Ile in hNa<sub>v</sub>1.3 (position 830 according to hNa<sub>v</sub>1.3 coordinates, 840 according to hNa<sub>v</sub>1.1 coordinates) differs from the Phe found in other neuronal isoforms, this residue is not present within the paddle motif and may not be accessible to Tf2. The Ser at position 842 (hNa<sub>v</sub>1.3 coordinates—indicated in red) is unique among hNa<sub>v</sub>1.1–1.3.</p
<p>(A) The nucleotide sequence of Tf2 was obtained by HiSeq (Illumina, USA). Signal peptide... more <p>(A) The nucleotide sequence of Tf2 was obtained by HiSeq (Illumina, USA). Signal peptide is underlined, mature peptide is highlighted in gray, and the amidation set point is marked in italic. (B) Multiple sequence alignment of Tf2 with other Na<sub>v</sub> channel toxins. Toxins are presented by their short names and UniProt KB codes. Capital letters denote amino acids. Lower-case letters denote: h, hydrophobic; s, small; b, big; p, polar; t, tiny; a, aromatic; l, aliphatic. Positive (+) and negative (-) amino acid residues that are part of the consensus sequence are also colored. Cys residues are shaded in black. aa means amino acid residues, and %Id is the percentage of sequence identity with Tf2.</p
<p>(A) Structural alignment between Tf2 (in blue) and five other Na<sub>v</sub>... more <p>(A) Structural alignment between Tf2 (in blue) and five other Na<sub>v</sub> channel scorpion toxins—Ts1, Ts2, CssII, CssIV, and AaHII (in gray). (B) Comparison of electrostatic potentials between the toxins Tf2, Ts1, Ts2, CssII, CssIV, and AaHII. The figure shows charge distribution along the toxin surface, divided into faces A and B. Shown in red are acidic residues whereas blue represents basic residues; in white, neutral regions are shown.</p
Biochimica et Biophysica Acta (BBA) - General Subjects, 2014
The venoms of several scorpion species have long been associated with pancreatitis in animal mode... more The venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. The cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. Antarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, sharing relevant structural elements with previously reported metalloproteases of the ADAM family. The phylogenetic analysis reveals that the reported sequences cluster in groups that correlate with the geographical localization of the respective species. Antareases are ubiquitous to a broad range of scorpion species, where they could be catalytically active enzymes. These molecules can be used to describe the evolution of scorpion venoms under different ecogeographic constrains. For the first time the complete sequence of the antareases is reported. It is demonstrated that antareases are common in the venom of different scorpion species. They are now proposed as targets for antivenom therapies.
Dissertação(mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, 2010. A peçonha... more Dissertação(mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, 2010. A peçonha de aranhas tem provado ser uma fonte valiosa de componentes farmacologicamente ativos capazes de exercer as mais diversas funções. Por atuarem em diferentes sistemas biológicos, a caracterização de componentes bioativos desperta grande interesse na prospecção de novos fármacos. Poucos trabalhos com aranhas caranguejeiras brasileiras têm sido desenvolvidos nessa área e nenhum até o momento foi realizado com a peçonha de Nhandu coloratovillosus. O presente trabalho teve como objetivo caracterizar a composição bioquímica da peçonha de N. coloratovillosus visando à identificação de compostos bioativos. A peçonha bruta foi submetida a fracionamento por RP-HPLC e 35 frações foram eluídas. Análises por MALDI-TOF MS detectaram a presença de 46 componentes de massas moleculares distintas. Por meio de eletroforese foi possível visualizar a presença de componentes de alta massa molecular. Um compo...
Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater ... more Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by Pimelodus maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 μg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 μg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus.
The venoms of several scorpion species have long been associated with pancreatitis in animal mode... more The venoms of several scorpion species have long been associated with pancreatitis in animal models and humans. Antarease, a Zn-metalloprotease from Tityus serrulatus, is able to penetrate intact pancreatic tissue and disrupts the normal vesicular traffic necessary for secretion, so it could play a relevant role in the onset of acute pancreatitis. The cDNA libraries from five different scorpion species were screened for antarease homologs with specific primers. The amplified PCR products were cloned and sequenced. A structural model was constructed to assess the functionality of the putative metalloproteases. A phylogenetic analysis was performed to identify clustering patterns of these venom components. Antarease-like sequences were amplified from all the screened cDNA libraries. The complete sequence of the antarease from T. serrulatus was obtained. The structural model of the putative antarease from Tityus trivittatus shows that it may adopt a catalytically active conformation, s...
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