Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis
Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A (OTA). Our prior research has indicated that ursolic acid (UA), which is widely present in fruits and medicinal plants, has the potential to alleviate nephrotoxicity triggered by OTA. Additionally, excessive indu...
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| Format: | Article |
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Tsinghua University Press
2025-04-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2024.9250181 |
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| author | Huiqiong Deng Wenying Chen Lingyun Han Boyang Zhang Xun Luo Song Yao Hongwei Wang Yao Zhou Shuangchao Liu Xiao Li Shen |
| author_facet | Huiqiong Deng Wenying Chen Lingyun Han Boyang Zhang Xun Luo Song Yao Hongwei Wang Yao Zhou Shuangchao Liu Xiao Li Shen |
| author_sort | Huiqiong Deng |
| collection | DOAJ |
| description | Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A (OTA). Our prior research has indicated that ursolic acid (UA), which is widely present in fruits and medicinal plants, has the potential to alleviate nephrotoxicity triggered by OTA. Additionally, excessive induction of endoplasmic reticulum (ER)-phagy exacerbates OTA-induced apoptosis. Therefore, further investigation is essential to comprehend whether UA can mitigate OTA-induced apoptosis by influencing ER-phagy. This objective is accomplished through a series of experiments involving assessments of cell viability, apoptosis, fluorescence microscopy, and western blot analysis. The outcomes of these experiments reveal that pre-treatment with 4 μmol/L UA for 2 h can markedly reverse the elevated apoptotic rate, the co-localization of ER and lysosomes, and the protein expressions of GRP78, p-eIF2α, Chop, Bax, and Bak, as well as the reduced cell viability and the protein expressions of Lonp1, Trap1, p62, Tex264, FAM134B, Bcl-2, and Bcl-xl, all caused by exposure to 1 μmol/L OTA for 24 h in human proximal tubule epithelial-originated kidney-2 (HK-2) cells (P < 0.05). Interestingly, the increased expression of LC3B-II induced by OTA is further amplified by UA pre-treatment (P < 0.05). In conclusion, OTA triggers a harmful feedback loop between ER stress (ERS) and excessive ER-phagy, thereby further promoting ERS- and mitochondrial-mediated apoptosis in vitro. However, this effect is significantly mitigated by UA through the inhibition of autophagosome-lysosome fusion, consequently blocking the excessive ER-phagic flux. |
| format | Article |
| id | doaj-art-c548fb6f70f64bf1b7a28d3edaae48a9 |
| institution | DOAJ |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-c548fb6f70f64bf1b7a28d3edaae48a92025-08-20T02:41:14ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302025-04-01144925018110.26599/FSHW.2024.9250181Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosisHuiqiong Deng0Wenying Chen1Lingyun Han2Boyang Zhang3Xun Luo4Song Yao5Hongwei Wang6Yao Zhou7Shuangchao Liu8Xiao Li Shen9School of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaResearch and Development Department, Allife Medicine Inc., Beijing 100176, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi 563000, ChinaFoods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A (OTA). Our prior research has indicated that ursolic acid (UA), which is widely present in fruits and medicinal plants, has the potential to alleviate nephrotoxicity triggered by OTA. Additionally, excessive induction of endoplasmic reticulum (ER)-phagy exacerbates OTA-induced apoptosis. Therefore, further investigation is essential to comprehend whether UA can mitigate OTA-induced apoptosis by influencing ER-phagy. This objective is accomplished through a series of experiments involving assessments of cell viability, apoptosis, fluorescence microscopy, and western blot analysis. The outcomes of these experiments reveal that pre-treatment with 4 μmol/L UA for 2 h can markedly reverse the elevated apoptotic rate, the co-localization of ER and lysosomes, and the protein expressions of GRP78, p-eIF2α, Chop, Bax, and Bak, as well as the reduced cell viability and the protein expressions of Lonp1, Trap1, p62, Tex264, FAM134B, Bcl-2, and Bcl-xl, all caused by exposure to 1 μmol/L OTA for 24 h in human proximal tubule epithelial-originated kidney-2 (HK-2) cells (P < 0.05). Interestingly, the increased expression of LC3B-II induced by OTA is further amplified by UA pre-treatment (P < 0.05). In conclusion, OTA triggers a harmful feedback loop between ER stress (ERS) and excessive ER-phagy, thereby further promoting ERS- and mitochondrial-mediated apoptosis in vitro. However, this effect is significantly mitigated by UA through the inhibition of autophagosome-lysosome fusion, consequently blocking the excessive ER-phagic flux.https://www.sciopen.com/article/10.26599/FSHW.2024.9250181ochratoxin aursolic acidendoplasmic reticulum (er) stresser-phagyer-phagic fluxapoptosis |
| spellingShingle | Huiqiong Deng Wenying Chen Lingyun Han Boyang Zhang Xun Luo Song Yao Hongwei Wang Yao Zhou Shuangchao Liu Xiao Li Shen Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis Food Science and Human Wellness ochratoxin a ursolic acid endoplasmic reticulum (er) stress er-phagy er-phagic flux apoptosis |
| title | Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis |
| title_full | Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis |
| title_fullStr | Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis |
| title_full_unstemmed | Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis |
| title_short | Ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin A-induced endoplasmic reticulum stress- and mitochondrial-mediated apoptosis |
| title_sort | ursolic acid inhibiting excessive reticulophagic flux contributes to alleviate ochratoxin a induced endoplasmic reticulum stress and mitochondrial mediated apoptosis |
| topic | ochratoxin a ursolic acid endoplasmic reticulum (er) stress er-phagy er-phagic flux apoptosis |
| url | https://www.sciopen.com/article/10.26599/FSHW.2024.9250181 |
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