Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells

Arsenault, Jason, Cuijpers, Sabine A. G., Ferrari, Enrico , Niranjan, Dhevahi, Rust, Aleksander, Leese, Charlotte, O'Brien, John A., Binz, Thomas and Davletov, Bazbek (2014) Botulinum protease-cleaved SNARE fragments induce cytotoxicity in neuroblastoma cells. Journal of Neurochemistry, 129 (5). pp. 781-791. ISSN 0022-3042

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.SNAREs (Soluble N-ethylmaleimide sensitive factor attachment protein receptors) are crucial for exocytosis, trafficking, and neurite outgrowth, where vesicular SNAREs are directed towards their partner target SNAREs: SNAP25 and syntaxin. SNARE proteins are normally membrane bound but can be cleaved and released by botulinum neurotoxins (BoNTs). We found that botulinum proteases types C and D can easily be transduced into endocrine cells using DNA-transfection reagents. Following administration of the C and D proteases into normally refractory Neuro2A neuroblastoma cells, the SNARE proteins were cleaved with high efficiency within hours. Remarkably, botulinum protease exposures led to cytotoxicity evidenced by spectrophotometric assays and propidium iodide penetration into the nuclei. Direct delivery of SNARE fragments into the neuroblastoma cells reduced viability similar to botulinum proteases’ application. We observed synergistic cytotoxic effects of the botulinum proteases, which may be explained by the release and interaction of soluble SNARE fragments. We show for the first time that previously observed cytotoxicity of BoNT/C in neurons could be achieved in cells of neuroendocrine origin with implications for medical uses of botulinum preparations.

Keywords:Neuroblastoma, SNARE, Botulinum, Syntaxin, Neuro2A, Cytotoxicity, Transfection reagents, JCOpen
Subjects:B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology
Divisions:College of Science > School of Life Sciences
ID Code:12812
Deposited On:06 Jan 2014 14:10

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