Novel components of Tityus serrulatus venom: A transcriptomic approach

Kalapothakis, Yan; Miranda, Kelton Gonçalves; Pereira, Adriana Heloísa; Witt, Amanda Stephanie Arantes; Marani, Camila; Martins, Ana Paula Vimieiro; Leal, Hortênsia Gomes; Campos-Júnior, Edimar; Pimenta, Adriano M.C.; Borges, Adolfo; Chávez-Olortégui, Carlos; Kalapothakis, Evanguedes

doi:10.1016/j.toxicon.2020.11.001

Cited by 18 publications

(14 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pimenta and collaborators (2001) [ 15 ] described the Tityus bahiensis Tb2-II (P60276) activity in mammals and in insects. Tityus serrulatus Ts2 (P68410) is a α-NaScTx and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission [ 16 ]. It has been shown the specificity and selectivity of Ts2 for some mammalian sodium channels inhibiting rapid inactivation of Na V 1.2, Na V 1.3, Na V 1.5, Na V 1.6 and Na V 1.7, but does not affect Na V 1.4, Na V 1.8 or the insect sodium channel ( Drosophila melanogaster sodium channel - DmNa V 1) [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the first two toxins isolated from the venom of the ancient scorpion Tityus (Archaeotityus) mattogrossensis (Borelli, 1901)

Oliveira¹,

Magalhães²,

Bloch

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

Background: Almost all Tityus characterized toxins are from subgenera Atreus and Tityus , there are only a few data about toxins produced by Archaeotityus , an ancient group in Tityus genus. Methods: Tityus (Archaeotityus) mattogrossensis crude venom was fractionated by high performance liquid chromatography, the major fractions were tested in a frog sciatic nerve single sucrose-gap technique. Two fractions (Tm1 and Tm2) were isolated, partially sequenced by MALDI-TOF/MS and electrophysiological assayed on HEK293 Nav 1.3, HEK293 Nav 1.6, DUM and DRG cells. Results: The sucrose-gap technique showed neurotoxicity in four fractions. One fraction caused a delay of action potential repolarization and other three caused a reduction in amplitude. An electrophysiological assay showed that Tm1 is active on HEK293 Nav 1.3, HEK293 Nav 1.6, DUM and DRG cells, and Tm2 on HEK293 Nav 1.3 and DRG cells, but not in HEK293 Nav 1.6. In addition, Tm1 and Tm2 did promote a shift to more negative potentials strongly suggesting that both are α-NaScTx. Conclusion: Although Tityus (Archaeotityus) mattogrossensis is considered an ancient group in Tityus genus, the primary structure of Tm1 and Tm2 is more related to Tityus subgenus. The patch clamp electrophysiological tests suggest that Tm1 and Tm2 are NaScTx, and also promoted no shift to more negative potentials, strongly suggesting that both are α-NaScTx. This paper aimed to explore and characterize for the first time toxins from the ancient scorpion Tityus (Archaeotityus) mattogrossensis.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of the first two toxins isolated from the venom of the ancient scorpion Tityus (Archaeotityus) mattogrossensis (Borelli, 1901)

Oliveira¹,

Magalhães²,

Bloch

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

View full text Add to dashboard Cite

show abstract

“…4), which is a peptide with high homology to Ts3 and Ts17 from T. serrulatus and Tb3 from T. bahiensis. These are α-mammal Na + channel modulating toxins (Kalapothakis et al, 2021).…”

Section: Identi Cation and Evolutionary Relationships Of Venom Ion Ch...mentioning

confidence: 99%

“…In addition, we were also able to identify two peptides whose partial sequences show homology to Na + channel modulating toxins found in T. serrulatus, and associated with α-subunits of lipolysis-activating peptides Ts28 and Ts41 (Fig. 6) (Kalapothakis et al, 2021). We named them Toc9 and Toc10 and even when it is suggested they probably act on Na + channels, they were not included in the phylogenetic analysis.…”

Section: Identi Cation and Evolutionary Relationships Of Venom Ion Ch...mentioning

confidence: 99%

“…However, results from our analyses show that in T. ocelote, venom is more complex than expected and has a composition at least comparable to that found in other Tityus species. It combines a variety of proteins and a group of cysteine-containing peptides that potentially act as modulators of ion channels, inducing neurotoxic effects (Guerrero-Vargas et al, 2012; de Oliveira et al, 2015;2018;Ortiz and Possani, 2018;Kalapothakis et al, 2021). It also has particularities that make it worth mentioning.…”

Section: Venom Compositionmentioning

confidence: 99%

See 1 more Smart Citation

Venomics of the Scorpion Tityus ocelote (Scorpiones, Buthidae): Understanding Venom Evolution in the Subgenus Archaeotityus

Díaz

Chang-Castillo

Lomonte

et al. 2022

Int J Pept Res Ther

View full text Add to dashboard Cite

The subgenus Tityus (Archaeotityus) includes small variegated species considered until recently, a basal group within Tityus, one of the most diverse and medically relevant genera of scorpions in the New World. Archaeotityus species are distributed in the humid forests of Lower Central America and the Choco, Guiana Shield, and Amazon regions. Due to their size and habits, Archaeotityus species are not usually considered dangerous, however, there are some clinical reports that show otherwise. To contribute to the toxinological knowledge of these poorly explored species, we characterized the venom of Tityus ocelote from three localities in Costa Rica. In addition, we assessed the evolutionary relationships of putative sodium channel modulating peptides found in this species with those reported for other members of the genus, through a maximum likelihood phylogenetic analysis based on their amino acid sequences.We observed the presence of homologs of previously identi ed NaTx from the species T. (Archaeotityus) clathratus and some other putative Na + and K + channel modulating peptides related to the T. bahiensis group. In addition, we sequenced some peptides related to toxins present in the venom of the subgenus Atreus, such as those reported T. obscurus, T. pachyurus, and the Costa Rican endemic species T. dedoslargos. Our phylogenetic analysis suggests that the venom of this Archaeotityus species is very complex and that some of the ion channel toxins expressed in it are related to distinct lineages within the genus Tityus, which could represent a plesiomorphic condition conserved in this group of scorpions of the New World.

show abstract

“…Cancer is characterized by prominent features including: increased cell proliferation, escape of growth inhibition, and high resistance to cell death [ 2 ]. Combining chemotherapy, radiation therapy, and surgery has proven to be the gold standard in cancer treatment, but it is accompanied by devastating side effects and toxicity, as well as a low degree of specificity [ 3 ]. Additionally, many classic anticancer drugs are unable to distinguish between normal and cancerous cells, which can lead to systemic toxicity and various side effects [ 4 ] although some efforts have accomplished the lowering of the toxicity of chemotherapeutics or have found a new way to comply with cancer such as ferroptosis [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, Hemiscorpius lepturus

et al. 2022

View full text Add to dashboard Cite

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.

show abstract

Novel components of Tityus serrulatus venom: A transcriptomic approach

Cited by 18 publications

References 92 publications

Characterization of the first two toxins isolated from the venom of the ancient scorpion Tityus (Archaeotityus) mattogrossensis (Borelli, 1901)

Characterization of the first two toxins isolated from the venom of the ancient scorpion Tityus (Archaeotityus) mattogrossensis (Borelli, 1901)

Venomics of the Scorpion Tityus ocelote (Scorpiones, Buthidae): Understanding Venom Evolution in the Subgenus Archaeotityus

Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, Hemiscorpius lepturus

Contact Info

Product

Resources

About