Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells
As one of the most important conjugated mycotoxins, zearalenone-14-glucoside (Z14G) has received widespread attention from researchers. Although the metabolism of Z14G in animals has been extensively studied, the intracellular toxicity and metabolic process of Z14G are not fully elucidated. In this...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Toxins |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6651/14/7/458 |
| _version_ | 1827603766609707008 |
|---|---|
| author | Haonan Ruan Yunyun Wang Yong Hou Jing Zhang Jiashuo Wu Fangqing Zhang Ming Sui Jiaoyang Luo Meihua Yang |
| author_facet | Haonan Ruan Yunyun Wang Yong Hou Jing Zhang Jiashuo Wu Fangqing Zhang Ming Sui Jiaoyang Luo Meihua Yang |
| author_sort | Haonan Ruan |
| collection | DOAJ |
| description | As one of the most important conjugated mycotoxins, zearalenone-14-glucoside (Z14G) has received widespread attention from researchers. Although the metabolism of Z14G in animals has been extensively studied, the intracellular toxicity and metabolic process of Z14G are not fully elucidated. In this study, the cytotoxicity of Z14G to human ovarian granulosa cells (KGN) and the metabolism of Z14G in KGN cells were determined. Furthermore, the experiments of co-administration of β-glucosidase and pre-administered β-glucosidase inhibitor (Conduritol B epoxide, CBE) were used to clarify the mechanism of Z14G toxicity release. Finally, the human colon adenocarcinoma cell (Caco-2) metabolism model was used to verify the toxicity release mechanism of Z14G. The results showed that the IC<sub>50</sub> of Z14G for KGN cells was 420 μM, and the relative hydrolysis rate of Z14G on ZEN was 35% (25% extracellular and 10% intracellular in KGN cells). The results indicated that Z14G cannot enter cells, and Z14G is only hydrolyzed extracellularly to its prototype zearalenone (ZEN) by β-glucosidase which can exert toxic effects in cells. In conclusion, this study demonstrated the cytotoxicity of Z14G and clarified the toxicity release mechanism of Z14G. Different from previous findings, our results showed that Z14G cannot enter cells but exerts cytotoxicity through deglycosylation. This study promotes the formulation of a risk assessment and legislation limit for ZEN and its metabolites. |
| first_indexed | 2024-03-09T05:46:16Z |
| format | Article |
| id | doaj.art-898a5ba9f89d4ea0a8fbe0bf8179bfc7 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T05:46:16Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-898a5ba9f89d4ea0a8fbe0bf8179bfc72023-12-03T12:21:04ZengMDPI AGToxins2072-66512022-07-0114745810.3390/toxins14070458Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN CellsHaonan Ruan0Yunyun Wang1Yong Hou2Jing Zhang3Jiashuo Wu4Fangqing Zhang5Ming Sui6Jiaoyang Luo7Meihua Yang8Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaKey Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, ChinaAs one of the most important conjugated mycotoxins, zearalenone-14-glucoside (Z14G) has received widespread attention from researchers. Although the metabolism of Z14G in animals has been extensively studied, the intracellular toxicity and metabolic process of Z14G are not fully elucidated. In this study, the cytotoxicity of Z14G to human ovarian granulosa cells (KGN) and the metabolism of Z14G in KGN cells were determined. Furthermore, the experiments of co-administration of β-glucosidase and pre-administered β-glucosidase inhibitor (Conduritol B epoxide, CBE) were used to clarify the mechanism of Z14G toxicity release. Finally, the human colon adenocarcinoma cell (Caco-2) metabolism model was used to verify the toxicity release mechanism of Z14G. The results showed that the IC<sub>50</sub> of Z14G for KGN cells was 420 μM, and the relative hydrolysis rate of Z14G on ZEN was 35% (25% extracellular and 10% intracellular in KGN cells). The results indicated that Z14G cannot enter cells, and Z14G is only hydrolyzed extracellularly to its prototype zearalenone (ZEN) by β-glucosidase which can exert toxic effects in cells. In conclusion, this study demonstrated the cytotoxicity of Z14G and clarified the toxicity release mechanism of Z14G. Different from previous findings, our results showed that Z14G cannot enter cells but exerts cytotoxicity through deglycosylation. This study promotes the formulation of a risk assessment and legislation limit for ZEN and its metabolites.https://www.mdpi.com/2072-6651/14/7/458zearalenone-14-glucosideUHPLC-ESI-MS/MSβ-glucosidasemetabolismtoxic release mechanism |
| spellingShingle | Haonan Ruan Yunyun Wang Yong Hou Jing Zhang Jiashuo Wu Fangqing Zhang Ming Sui Jiaoyang Luo Meihua Yang Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells Toxins zearalenone-14-glucoside UHPLC-ESI-MS/MS β-glucosidase metabolism toxic release mechanism |
| title | Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells |
| title_full | Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells |
| title_fullStr | Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells |
| title_full_unstemmed | Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells |
| title_short | Zearalenone-14-Glucoside Is Hydrolyzed to Zearalenone by β-Glucosidase in Extracellular Matrix to Exert Intracellular Toxicity in KGN Cells |
| title_sort | zearalenone 14 glucoside is hydrolyzed to zearalenone by β glucosidase in extracellular matrix to exert intracellular toxicity in kgn cells |
| topic | zearalenone-14-glucoside UHPLC-ESI-MS/MS β-glucosidase metabolism toxic release mechanism |
| url | https://www.mdpi.com/2072-6651/14/7/458 |
| work_keys_str_mv | AT haonanruan zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT yunyunwang zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT yonghou zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT jingzhang zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT jiashuowu zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT fangqingzhang zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT mingsui zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT jiaoyangluo zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells AT meihuayang zearalenone14glucosideishydrolyzedtozearalenonebybglucosidaseinextracellularmatrixtoexertintracellulartoxicityinkgncells |