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Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells

Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider L. tredecimguttatus. To explore the mechanism of action of the LETX-VI on nerve cells, the effects of LETX-VI on PC12 cells, a commonly used neuron model, were analyzed using a pull-down assay-guided strategy. LET...

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Autores principales: Tang, Xiaochao, Yu, Dianmei, Wang, Haiyan, Meng, Wenwen, Zhai, Yiwen, Lei, Zhixiang, Liu, Zhen, Wang, Xianchun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918074/
https://www.ncbi.nlm.nih.gov/pubmed/33673184
http://dx.doi.org/10.3390/toxins13020136
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author Tang, Xiaochao
Yu, Dianmei
Wang, Haiyan
Meng, Wenwen
Zhai, Yiwen
Lei, Zhixiang
Liu, Zhen
Wang, Xianchun
author_facet Tang, Xiaochao
Yu, Dianmei
Wang, Haiyan
Meng, Wenwen
Zhai, Yiwen
Lei, Zhixiang
Liu, Zhen
Wang, Xianchun
author_sort Tang, Xiaochao
collection PubMed
description Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider L. tredecimguttatus. To explore the mechanism of action of the LETX-VI on nerve cells, the effects of LETX-VI on PC12 cells, a commonly used neuron model, were analyzed using a pull-down assay-guided strategy. LETX-VI was shown to interact with 164 PC12 cell proteins that have diverse molecular functions such as binding, catalysis, regulation, structural activity, etc., thereby extensively affecting the biological processes in the PC12 cells, particularly protein metabolism, response to stimulus, substance transport, and nucleic acid metabolism, with 56.71%, 42.07%, 29.88% and 28.66% of the identified proteins being involved in these biological processes, respectively. By interacting with the relevant proteins, LETX-VI enhanced the synthesis of dopamine; positively regulated cell division and proliferation; and negatively regulated cell cycle arrest, cell death, and apoptotic processes, and therefore has limited cytotoxicity against the PC12 cells, which were further experimentally confirmed. In general, the effects of LETX-VI on PC12 cells are more regulatory than cytotoxic. These findings have deepened our understanding of the action mechanism of LETX-VI on nerve cells and provided valuable clues for further related researches including those on Parkinson’s disease.
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spelling pubmed-79180742021-03-02 Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells Tang, Xiaochao Yu, Dianmei Wang, Haiyan Meng, Wenwen Zhai, Yiwen Lei, Zhixiang Liu, Zhen Wang, Xianchun Toxins (Basel) Article Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider L. tredecimguttatus. To explore the mechanism of action of the LETX-VI on nerve cells, the effects of LETX-VI on PC12 cells, a commonly used neuron model, were analyzed using a pull-down assay-guided strategy. LETX-VI was shown to interact with 164 PC12 cell proteins that have diverse molecular functions such as binding, catalysis, regulation, structural activity, etc., thereby extensively affecting the biological processes in the PC12 cells, particularly protein metabolism, response to stimulus, substance transport, and nucleic acid metabolism, with 56.71%, 42.07%, 29.88% and 28.66% of the identified proteins being involved in these biological processes, respectively. By interacting with the relevant proteins, LETX-VI enhanced the synthesis of dopamine; positively regulated cell division and proliferation; and negatively regulated cell cycle arrest, cell death, and apoptotic processes, and therefore has limited cytotoxicity against the PC12 cells, which were further experimentally confirmed. In general, the effects of LETX-VI on PC12 cells are more regulatory than cytotoxic. These findings have deepened our understanding of the action mechanism of LETX-VI on nerve cells and provided valuable clues for further related researches including those on Parkinson’s disease. MDPI 2021-02-12 /pmc/articles/PMC7918074/ /pubmed/33673184 http://dx.doi.org/10.3390/toxins13020136 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tang, Xiaochao
Yu, Dianmei
Wang, Haiyan
Meng, Wenwen
Zhai, Yiwen
Lei, Zhixiang
Liu, Zhen
Wang, Xianchun
Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title_full Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title_fullStr Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title_full_unstemmed Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title_short Pull-Down Assay-Guided Insights into the Effects of Latroeggtoxin-VI on Nerve Cells
title_sort pull-down assay-guided insights into the effects of latroeggtoxin-vi on nerve cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918074/
https://www.ncbi.nlm.nih.gov/pubmed/33673184
http://dx.doi.org/10.3390/toxins13020136
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