Phosphoproteomics reveals NMDA receptor-mediated excitotoxicity as a key signaling pathway in the toxicity of gelsenicine
Copyright © 2021 Elsevier Ltd. All rights reserved..
Gelsenicine is one of the most toxic compounds in the genus Gelsemium, but the mechanism of toxicity is not clear. In this paper, tandem mass tag quantitative phosphoproteomics was used to study the changes in protein phosphorylation in different brain regions at different time points after gelsenicine poisoning in mice. The correlation between neurotransmitter receptors and the toxicity of gelsenicine was analyzed by molecular docking and rescue experiments. Parallel reaction monitoring (PRM) was used to verify the related proteins. A total of 17877 unique phosphosites were quantified and mapped to 4170 brain proteins to understand the signaling pathways. Phosphoproteomics revealed gelsenicine poisoning mainly affected protein phosphorylation levels in the hippocampus, and through bioinformatics analysis, it was found gelsenicine poisoning significantly affected neurotransmitter synaptic pathway. The molecular docking results showed that gelsenicine could bind to the N-methyl-D-aspartic acid receptor (NMDAR). In addition, we found that NMDA was effective in improving the survival rate of the animals tested, and this effect was associated with reduced protein phosphorylation by PRM validation. The results revealed that gelsenicine affects neurotransmitter release and receptor function. This is the first demonstration that NMDA receptor-mediated excitotoxicity is a key signaling pathway in the toxicity of gelsenicine.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:156 |
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| Enthalten in: |
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association - 156(2021) vom: 01. Okt., Seite 112507 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Si-Juan [VerfasserIn] |
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| Links: |
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| Themen: |
6384-92-5 |
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| Anmerkungen: |
Date Completed 27.12.2021 Date Revised 27.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.fct.2021.112507 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329331337 |
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| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Gelsenicine is one of the most toxic compounds in the genus Gelsemium, but the mechanism of toxicity is not clear. In this paper, tandem mass tag quantitative phosphoproteomics was used to study the changes in protein phosphorylation in different brain regions at different time points after gelsenicine poisoning in mice. The correlation between neurotransmitter receptors and the toxicity of gelsenicine was analyzed by molecular docking and rescue experiments. Parallel reaction monitoring (PRM) was used to verify the related proteins. A total of 17877 unique phosphosites were quantified and mapped to 4170 brain proteins to understand the signaling pathways. Phosphoproteomics revealed gelsenicine poisoning mainly affected protein phosphorylation levels in the hippocampus, and through bioinformatics analysis, it was found gelsenicine poisoning significantly affected neurotransmitter synaptic pathway. The molecular docking results showed that gelsenicine could bind to the N-methyl-D-aspartic acid receptor (NMDAR). In addition, we found that NMDA was effective in improving the survival rate of the animals tested, and this effect was associated with reduced protein phosphorylation by PRM validation. The results revealed that gelsenicine affects neurotransmitter release and receptor function. This is the first demonstration that NMDA receptor-mediated excitotoxicity is a key signaling pathway in the toxicity of gelsenicine | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gelsemium | |
| 650 | 4 | |a Gelsenicine | |
| 650 | 4 | |a NMDAR | |
| 650 | 4 | |a Phosphoproteomic | |
| 650 | 4 | |a Toxicity | |
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| 650 | 7 | |a Indole Alkaloids |2 NLM | |
| 650 | 7 | |a Receptors, N-Methyl-D-Aspartate |2 NLM | |
| 650 | 7 | |a gelsenicine |2 NLM | |
| 650 | 7 | |a N-Methylaspartate |2 NLM | |
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| 700 | 1 | |a Qi, Xue-Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chong-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhao-Ying |e verfasserin |4 aut | |
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