Protein toxins of the Echis coloratus viper venom directly activate TRPV1
| Autor: | Philip Lazarovici, Avi Priel, Matan Geron, Rakesh Kumar, Adi Lahiani, Gadi Cohen, Henry Matzner, Galit Gincberg |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Biophysics TRPV1 Heterologous TRPV Cation Channels Venom Peptide Receptors Nerve Growth Factor Viper Venoms complex mixtures Biochemistry Cell Line 03 medical and health sciences Nerve Growth Factor Viperidae Animals Humans Receptor Molecular Biology Toxins Biological chemistry.chemical_classification Neurons Binding Sites biology HEK 293 cells Proteins biology.organism_classification Molecular biology Echis coloratus Cell biology 030104 developmental biology HEK293 Cells nervous system chemistry Calcium |
| Zdroj: | Biochimica et biophysica acta. General subjects. 1861(3) |
| ISSN: | 0304-4165 |
| Popis: | Background Peptide and protein toxins are essential tools to dissect and probe the biology of their target receptors. Venoms target vital physiological processes to evoke pain. Snake venoms contain various factors with the ability to evoke, enhance and sustain pain sensation. While a number of venom-derived toxins were shown to directly target TRPV1 channels expressed on somatosensory nerve terminals to evoke pain response, such toxins were yet to be identified in snake venoms. Methods We screened Echis coloratus saw-scaled viper venom's protein fractions isolated by reversed phase HPLC for their ability to activate TRPV1 channels. To this end, we employed heterologous systems to analyze TRPV1 and NGF pathways by imaging and electrophysiology, combined with molecular biology, biochemical, and pharmacological tools. Results We identified TRPV1 activating proteins in the venom of Echis coloratus that produce a channel-dependent increase in intracellular calcium and outwardly rectifying currents in neurons and heterologous systems. Interestingly, channel activation was not mediated by any of its known toxin binding sites. Moreover, although NGF neurotropic activity was detected in this venom, TRPV1 activation was independent of NGF receptors. Conclusions Echis coloratus venom contains proteins with the ability to directly activate TRPV1. This activity is independent of the NGF pathway and is not mediated by known TRPV1 toxins' binding sites. General significance Our results could facilitate the discovery of new toxins targeting TRPV1 to enhance current understanding of this receptor activation mechanism. Furthermore, the findings of this study provide insight into the mechanism through which snakes' venom elicit pain. |
| Databáze: | OpenAIRE |
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