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Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells

Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na(+),K(+)-ATPase, much still remains unclear about PLTX’s mechanism of ac...

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Autores principales: Cheng, Dingyuan, Deng, Bowen, Tong, Qiling, Gao, Siyi, Xiao, Boyi, Zhu, Mengxuan, Ren, Ziyu, Wang, Lianghua, Sun, Mingjuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031313/
https://www.ncbi.nlm.nih.gov/pubmed/35448878
http://dx.doi.org/10.3390/toxins14040269
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author Cheng, Dingyuan
Deng, Bowen
Tong, Qiling
Gao, Siyi
Xiao, Boyi
Zhu, Mengxuan
Ren, Ziyu
Wang, Lianghua
Sun, Mingjuan
author_facet Cheng, Dingyuan
Deng, Bowen
Tong, Qiling
Gao, Siyi
Xiao, Boyi
Zhu, Mengxuan
Ren, Ziyu
Wang, Lianghua
Sun, Mingjuan
author_sort Cheng, Dingyuan
collection PubMed
description Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na(+),K(+)-ATPase, much still remains unclear about PLTX’s mechanism of action. Here, we tested different concentrations of PLTX on HaCaT cells and studied its distributions in cells, its impact on gene expression, and the associated pathways via proteomics combined with bioinformatics tools. We found that PLTX could cause ferroptosis in HaCaT cells, a new type of programmed cell death, by up-regulating the expression of VDAC3, ACSL4 and NCOA4, which lead to the occurrence of ferroptosis. PLTX also acts on the MAPK pathway, which is related to cell apoptosis, proliferation, division and differentiation. Different from its effect on ferroptosis, PLTX down-regulates the expression of ERK, and, as a result, the expressions of MAPK1, MAP2K1 and MAP2K2 are also lower, affecting cell proliferation. The genes from these two mechanisms showed interactions, but we did not find overlap genes between the two. Both ferroptosis and MAPK pathways can be used as anticancer targets, so PLTX may become an anticancer drug with appropriate modification.
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spelling pubmed-90313132022-04-23 Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells Cheng, Dingyuan Deng, Bowen Tong, Qiling Gao, Siyi Xiao, Boyi Zhu, Mengxuan Ren, Ziyu Wang, Lianghua Sun, Mingjuan Toxins (Basel) Article Palytoxin (PLTX) is a polyether marine toxin isolated from sea anemones. It is one of the most toxic nonprotein substances, causing many people to be poisoned every year and to die in severe cases. Despite its known impact on Na(+),K(+)-ATPase, much still remains unclear about PLTX’s mechanism of action. Here, we tested different concentrations of PLTX on HaCaT cells and studied its distributions in cells, its impact on gene expression, and the associated pathways via proteomics combined with bioinformatics tools. We found that PLTX could cause ferroptosis in HaCaT cells, a new type of programmed cell death, by up-regulating the expression of VDAC3, ACSL4 and NCOA4, which lead to the occurrence of ferroptosis. PLTX also acts on the MAPK pathway, which is related to cell apoptosis, proliferation, division and differentiation. Different from its effect on ferroptosis, PLTX down-regulates the expression of ERK, and, as a result, the expressions of MAPK1, MAP2K1 and MAP2K2 are also lower, affecting cell proliferation. The genes from these two mechanisms showed interactions, but we did not find overlap genes between the two. Both ferroptosis and MAPK pathways can be used as anticancer targets, so PLTX may become an anticancer drug with appropriate modification. MDPI 2022-04-10 /pmc/articles/PMC9031313/ /pubmed/35448878 http://dx.doi.org/10.3390/toxins14040269 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Dingyuan
Deng, Bowen
Tong, Qiling
Gao, Siyi
Xiao, Boyi
Zhu, Mengxuan
Ren, Ziyu
Wang, Lianghua
Sun, Mingjuan
Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title_full Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title_fullStr Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title_full_unstemmed Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title_short Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells
title_sort proteomic studies of the mechanism of cytotoxicity, induced by palytoxin on hacat cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031313/
https://www.ncbi.nlm.nih.gov/pubmed/35448878
http://dx.doi.org/10.3390/toxins14040269
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