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Neurotoxicity fingerprinting of venoms using on-line microfluidic AChBP profiling.

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Slagboom, Julien, Otvos, Reka A, Cardoso, Fernanda C, Iyer, Janaki, Visser, Jeroen C, van Doodewaerd, Bjorn R, McCleary, Ryan J R, Niessen, Wilfried M A, Somsen, Govert W, Lewis, Richard J, Kini, R Manjunatha, Smit, August B, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719 and Kool, Jeroen (2018) 'Neurotoxicity fingerprinting of venoms using on-line microfluidic AChBP profiling.'. Toxicon, Vol 148, pp. 213-222.

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Abstract

Venoms from snakes are rich sources of highly active proteins with potent affinity towards a variety of enzymes and receptors. Of the many distinct toxicities caused by envenomation, neurotoxicity plays an important role in the paralysis of prey by snakes as well as by venomous sea snails and insects. In order to improve the analytical discovery component of venom toxicity profiling, this paper describes the implementation of microfluidic high-resolution screening (HRS) to obtain neurotoxicity fingerprints from venoms that facilitates identification of the neurotoxic components of envenomation. To demonstrate this workflow, 47 snake venoms were profiled using the acetylcholine binding protein (AChBP) to mimic the target of neurotoxic proteins, in particular nicotinic acetylcholine receptors (nAChRs). In the microfluidic HRS system, nanoliquid chromatographic (nanoLC) separations were on-line connected to both AChBP profiling and parallel mass spectrometry (MS). For virtually all neurotoxic elapid snake venoms tested, we obtained bioactivity fingerprints showing major and minor bioactive zones containing masses consistent with three-finger toxins (3FTxs), whereas, viperid and colubrid venoms showed little or no detectable bioactivity. Our findings demonstrate that venom interactions with AChBP correlate with the severity of neurotoxicity observed following human envenoming by different snake species. We further, as proof of principle, characterized bioactive venom peptides from a viperid (Daboia russelli) and an elapid (Aspidelaps scutatus scutatus) snake by nanoLC-MS/MS, revealing that different toxin classes interact with the AChBP, and that this binding correlates with the inhibition of α7-nAChR in calcium-flux cell-based assays. The on-line post-column binding assay and subsequent toxin characterization methodologies described here provide a new in vitro analytic platform for rapidly investigating neurotoxic snake venom proteins.

Item Type: Article
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QV Pharmacology > Autonomic Agents. Nonmetallic Elements. Neuromuscular Agents > QV 120 Autonomic agents
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins
WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
WL Nervous System > WL 100 General works
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1016/j.toxicon.2018.04.022
Depositing User: Stacy Murtagh
Date Deposited: 17 May 2018 15:55
Last Modified: 18 May 2018 10:32
URI: https://archive.lstmed.ac.uk/id/eprint/8616

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