Crotoxin: Novel activities for a classic β-neurotoxin

Sampaio, Sandra Coccuzzo; Hyslop, Stephen; Fontes, Marcos R.M.; Prado-Franceschi, J.; Zambelli, Vanessa O.; Magro, Ângelo J.; Brigatte, Patrícia; Gutierrez, Vanessa Pacciari; Cury, Yara

doi:10.1016/j.toxicon.2010.01.011

Cited by 123 publications

(110 citation statements)

References 157 publications

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“…Structurally, crotoxin is a heterodimeric β-neurotoxin that consists of a toxic basic phospholipase A 2 and a nonenzymatic, non-toxic acidic component (crotapotin). Crotapotin potentiates the activity of crotoxin, since it prevents the basic phospholipase subunit binding to non-specific sites (Sampaio et al, 2010;Soares et al, 2001). Crotoxin targets neuromuscular junctions and inhibits the release of acetylcholine, which leads to neuromuscular blockade and muscular and respiratory paralysis.…”

Section: Crotalus Venommentioning

confidence: 99%

“…Crotoxin targets neuromuscular junctions and inhibits the release of acetylcholine, which leads to neuromuscular blockade and muscular and respiratory paralysis. In the muscle tissue, crotoxin causes selective injury of skeletal muscle groups composed of type I and IIa fibers, which are extremely vascularized and rich in myoglobin (Sampaio et al, 2010). Other important toxins are crotamine, convulxin and gyroxin.…”

Section: Crotalus Venommentioning

confidence: 99%

See 1 more Smart Citation

Acute Kidney Injury Induced by Snake and Arthropod Venoms

Berger¹,

Vieira²,

Guimarães³

2012

Renal Failure - The Facts

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Section: Crotalus Venommentioning

confidence: 99%

Section: Crotalus Venommentioning

confidence: 99%

Acute Kidney Injury Induced by Snake and Arthropod Venoms

Berger¹,

Vieira²,

Guimarães³

2012

Renal Failure - The Facts

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“…Crotoxin was the first protein isolated and crystallized from animal venom [1,2]. a Crotoxin is a heterodimeric protein that consists of a non-toxic, nonenzymatic, acidic subunit (crotapotin, crotoxin A, CA) non-covalently associated with a weakly toxic, basic subunit (crotoxin B, CB) that expresses phospholipase A 2 activity.…”

Section: Introductionmentioning

confidence: 99%

“…Along with these well-known activities, several other biochemical and pharmacological effects have been reported, some of them highlighting the potential pharmaceutical use of this protein. These effects include the antibacterial, antiviral, anti-inflammatory, antitumoral, and analgesic activities of CTX and its subunits (CA and CB) [1,2].…”

Section: Introductionmentioning

confidence: 99%

Heterologous Expression and Purification of Recombinant Crotoxin B, the Phospholipase A2 Subunit of Crotoxin

Boda¹,

Salamon²,

Orbán³

et al. 2018

Studia UBB Chemia

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ABSTRACT.Crotoxin is a heterodimeric β-neurotoxin isolated from the venom of Crotalus durissus terrificus, consisting of two, non-covalently bound subunits, crotapotin (CA) and crotoxin B (CB). Both subunits present four different isoforms, consequently there are up to 16 different crotoxin complexes, each with different activity levels. The biological activities usually associated with crotoxin include neurotoxicity, myotoxicity and cardiotoxicity, however several other important biochemical and pharmacological effects of crotoxin have been observed, such as the antibacterial, antiviral, antiinflammatory, antitumoral and analgesic activity. In this study we present the production of recombinant crotoxin B (isoform C). Expression of the protein was carried out using E. coli Rosetta TM (DE3)pLysS strain, and the obtained protein was separated and purified using Ni 2+ -affinity chromatography. To the best of our knowledge the developed method represents the first reported method for obtaining the crotoxin B (isoform C) through heterologous expression using an efficient and cost-effective procedure.

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“…Crotalus durissus neurotoxin (crotoxin) is a nerve toxin isolated from South American diamondback snake subfamilies. Recent studies have indicated a potential antitumor effect of crotoxin [6,7] , although its specific mechanism remains unclear. In this study, we therefore investigated the antitumor effects of crotoxin in human esophageal carcinoma (Eca-109) cells and in a nude mouse tumor transplantation model.…”

Section: Introductionmentioning

confidence: 99%

Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice

Wang

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the antitumor actions of the Crotalus durissus neurotoxin (crotoxin) on human esophageal carcinoma (Eca-109) cells in vitro and transplanted esophageal Eca-109 tumors in nude mice. Methods: The growth-inhibitory effect was analyzed in Eca-109 cells using MTT assay. Cell morphology changes in nuclei were observed using Hoechst 33342 staining, while apoptosis and cell cycle distribution were examined by flow cytometry. RT-PCR was used to measure the Bcl-2, p15, and caspase-3 p17 gene expression levels. A tumor transplantation model was established by inoculation of Eca-109 cells were into female Balb/c nude mice. Crotoxin (25, 50, and 100 mg/kg) was subcutaneously injected into the transplanted tumors every 2 d for a total of 10 injections. Tumor size and weight were measured. Bcl-2, p15, and caspase-3 p17 protein expression in transplanted tumors was analyzed using Western blotting. Results: Crotoxin (25, 50, and 100 µg/mL) inhibited the growth of Eca-109 cells in a dose-dependent manner with inhibition rates of 22.9%, 35.8%, and 57.2%, respectively. Hoechst 33342 staining revealed apoptotic cells with pyknotic nuclear chromatin after crotoxin treatment. In Eca-109 cells, crotoxin induced apoptosis and G1 block, significantly upregulated the expression of p15 and caspase-3 p17 genes and downregulated the expression of Bcl-2 gene. Furthermore, crotoxin inhibited the growth of Eca-109 tumors in nude mice in a dose-dependent manner. Western blotting showed that crotoxin increased p15 and caspase-3 p17 protein levels and reduced Bcl-2 protein level in tumor specimens. Conclusion: Crotoxin inhibits the growth of Eca-109 cells in vitro via apoptosis induction and G 1 block. Local administration of crotoxin inhibits the growth of subcutaneously transplanted Eca-109 cells in nude mice, possibly via increasing p15 and caspase-3 p17 protein expression and reducing Bcl-2 protein expression.

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Crotoxin: Novel activities for a classic β-neurotoxin

Cited by 123 publications

References 157 publications

Acute Kidney Injury Induced by Snake and Arthropod Venoms

Acute Kidney Injury Induced by Snake and Arthropod Venoms

Heterologous Expression and Purification of Recombinant Crotoxin B, the Phospholipase A2 Subunit of Crotoxin

Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice

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