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Toxicon. 2013 Dec 15;76:37-43. doi: 10.1016/j.toxicon.2013.09.002. Epub 2013 Sep 15.

Mastoparan-7 rescues botulinum toxin-A poisoned neurons in a mouse spinal cord cell culture model.

Author information

1
Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.

Abstract

Botulinum neurotoxin serotype A (BoNT/A) is the most potent poison of biological origin known to mankind. The toxicity of BoNT/A is due to the inhibition of neurotransmission at cholinergic synapses; this is responsible for the symptom of flaccid paralysis at peripheral neuromuscular junctions. At a molecular level, the BoNT/A effect is due to its inhibition of stimulated acetylcholine (ACh) release from presynaptic nerve terminals. Currently, there is no antidote available to rescue BoNT/A-poisoned synapses. Here, we report an example of rescuing botulinum-poisoned cultured mouse spinal cord neurons by treatment with Mastoparan-7 (Mas-7), which is known to be a phospholipase A2 activator compound. Mas-7, a naturally occurring bee venom peptide, was delivered to botulinum-poisoned neurons via a drug delivery vehicle (DDV) construct prepared using the recombinant non-toxic heavy chain (HC) fragment of BoNT/A itself. In this method, the BoNT/A HC component in the DDV served as a neuron specific drug targeting molecule. We found that Mas-7 delivered into BoNT/A intoxicated spinal cord cells restored over 40% their property of stimulated neurotransmitter release. Rescue from cell poisoning did not occur from inhibition of the endopeptidase activity of BoNT/A light chain (LC) against its well-known substrate, SNAP-25 that is mechanistically involved in the cholinergic neuroexocytosis process. Rather, Mas-7 induced a physiological host response apparently unrelated to SNAP-25, but linked to the phospholipase-mediated signal transduction pathway.

KEYWORDS:

Botulinum neurotoxin; Drug delivery vehicle; Mastoparan-7; Neurons; Rescue of botulism

PMID:
24047963
DOI:
10.1016/j.toxicon.2013.09.002
[Indexed for MEDLINE]
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