Structural and Functional Interactions between Transient Receptor Potential Vanilloid Subfamily 1 and Botulinum Neurotoxin Serotype AReportar como inadecuado




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Background

Botulinum neurotoxins are produced by Clostridium botulinum bacteria. There are eight serologically distinct botulinum neurotoxin isoforms serotypes A–H. Currently, botulinum neurotoxin serotype A BoNT⁄A is commonly used for the treatment of many disorders, such as hyperactive musculoskeletal disorders, dystonia, and pain. However, the effectiveness of BoNT⁄A for pain alleviation and the mechanisms that mediate the analgesic effects of BoNT⁄A remain unclear. To define the antinociceptive mechanisms by which BoNT-A functions, the interactions between BoNT⁄A and the transient receptor potential vanilloid subfamily 1 TRPV1 were investigated using immunofluorescence, co-immunoprecipitation, and western blot analysis in primary mouse embryonic dorsal root ganglion neuronal cultures.

Results

1 Three-week-old cultured dorsal root ganglion neurons highly expressed transient TRPV1, synaptic vesicle 2A SV2A and synaptosomal-associated protein 25 SNAP-25. SV2A and SNAP-25 are the binding receptor and target protein, respectively, of BoNT⁄A. 2 TRPV1 colocalized with both BoNT⁄A and cleaved SNAP-25 when BoNT⁄A was added to dorsal root ganglia neuronal cultures. 3 After 24 hours of BoNT⁄A treatment 1 nmol⁄l, both TRPV1 and BoNT⁄A positive bands were detected in western blots of immunoprecipitated pellets. 4 Blocking TRPV1 with a specific antibody decreased the cleavage of SNAP-25 by BoNT⁄A.

Conclusion

BoNT-A interacts with TRPV1 both structurally and functionally in cultured mouse embryonic dorsal root ganglion neurons. These results suggest that an alternative mechanism is used by BoNT⁄A to mediate pain relief.



Autor: Xiaqing Li , Julie A. Coffield

Fuente: http://plos.srce.hr/



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