Dramatic neurological and biological effects by botulinum neurotoxin type A on SH-SY5Y neuroblastoma cells, beyond the b
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(2020) 21:66
RESEARCH ARTICLE
Open Access
Dramatic neurological and biological effects by botulinum neurotoxin type A on SH-SY5Y neuroblastoma cells, beyond the blockade of neurotransmitter release Lei Wang1, Carol S. Ringelberg2 and Bal R. Singh1,3*
Abstract Background: Gene expression profile analysis on mammalian cell lines and animal models after exposure to botulinum neurotoxin (BoNT) has been investigated in several studies in recent years. Microarray analysis provides a powerful tool for identifying critical signaling pathways involved in the biological and inflammatory responses to BoNT and helps determine the mechanism of the function of botulinum toxins. One of the pivotal clinical characteristics of BoNT is its prolonged on-site effects. The role of BoNT on the blockage of neurotransmitter acetylcholine release in the neuromuscular junction has been well established. However, the effects of the treatment time of BoNT on the human cellular model and its potential mechanism remain to be defined. Methods: This study aimed to use gene microarray technology to compare the two physiological critical time points of BoNT type A (BoNT/A) treatment of human neuroblastoma cells and to advance our understanding of the profound biological influences that toxin molecules play in the neuronal cellular system. SH-SY5Y neuroblastoma cells were treated with BoNT/A for 4 and 48 h, which represent the time needed for the entrance of toxin into the cells and the time necessary for the initial appearance of the on-site effects after BoNT application, respectively. Results: A comparison of the two time points identified 122 functional groups that are significantly changed. The top five groups are alternative splicing, phosphoprotein, nucleus, cytoplasm, and acetylation. Furthermore, after 48 h, there were 744 genes significantly up-regulated, and 624 genes significantly down-regulated (p‹ 0.01). These genes fell into the following neurological and biological annotation groups: Nervous system development, proteinaceous extracellular matrix, signaling pathways regulating pluripotency of stem cells, cellular function and signal transduction, and apoptosis. We have also noticed that the up-regulated groups contained neuronal cell development, nervous system development, and metabolic processes. In contrast, the down-regulated groups contained many chromosomes and cell cycle categories. (Continued on next page)
* Correspondence: [email protected] 1 Prime Bio, Inc., North Dartmouth, MA 02747, USA 3 Institute of Advanced Sciences, Botulinum Research Center, North Dartmouth, MA 02747, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were
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