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<sup>+</sup>,K<sup>+</sup>-ATPase, much still re...
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MDPI AG
2022-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/4/269 |
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| author | Dingyuan Cheng Bowen Deng Qiling Tong Siyi Gao Boyi Xiao Mengxuan Zhu Ziyu Ren Lianghua Wang Mingjuan Sun |
| author_facet | Dingyuan Cheng Bowen Deng Qiling Tong Siyi Gao Boyi Xiao Mengxuan Zhu Ziyu Ren Lianghua Wang Mingjuan Sun |
| author_sort | Dingyuan Cheng |
| collection | DOAJ |
| 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<sup>+</sup>,K<sup>+</sup>-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. |
| first_indexed | 2024-03-09T04:09:34Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T04:09:34Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-502c8d2c30154f3eb9af3828ced666b32023-12-03T14:01:56ZengMDPI AGToxins2072-66512022-04-0114426910.3390/toxins14040269Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT CellsDingyuan Cheng0Bowen Deng1Qiling Tong2Siyi Gao3Boyi Xiao4Mengxuan Zhu5Ziyu Ren6Lianghua Wang7Mingjuan Sun8Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaDepartment of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, ChinaPalytoxin (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<sup>+</sup>,K<sup>+</sup>-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.https://www.mdpi.com/2072-6651/14/4/269palytoxinproteomic analysisMAPKferroptosis |
| spellingShingle | Dingyuan Cheng Bowen Deng Qiling Tong Siyi Gao Boyi Xiao Mengxuan Zhu Ziyu Ren Lianghua Wang Mingjuan Sun Proteomic Studies of the Mechanism of Cytotoxicity, Induced by Palytoxin on HaCaT Cells Toxins palytoxin proteomic analysis MAPK ferroptosis |
| 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 | palytoxin proteomic analysis MAPK ferroptosis |
| url | https://www.mdpi.com/2072-6651/14/4/269 |
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