Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine
The necroptosis of granulosa cells has been proven to be one of the important triggers of follicular atresia, which is an important cause of reduced reproductive capacity in cows. The rapid growth of granulosa cells is accompanied by endoplasmic reticulum stress (ERS), leading to granulosa cell deat...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/6/419 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342994483773440 |
|---|---|
| author | Xiaorui Yang Yue Chen Xinzi Wang Gaoqing Xu Hongjie Wang Xinqi Shu He Ding Xin Ma Jing Guo Jun Wang Jing Zhao Yi Fang Hongyu Liu Wenfa Lu |
| author_facet | Xiaorui Yang Yue Chen Xinzi Wang Gaoqing Xu Hongjie Wang Xinqi Shu He Ding Xin Ma Jing Guo Jun Wang Jing Zhao Yi Fang Hongyu Liu Wenfa Lu |
| author_sort | Xiaorui Yang |
| collection | DOAJ |
| description | The necroptosis of granulosa cells has been proven to be one of the important triggers of follicular atresia, which is an important cause of reduced reproductive capacity in cows. The rapid growth of granulosa cells is accompanied by endoplasmic reticulum stress (ERS), leading to granulosa cell death. However, the link between ERS and necroptosis, as well as its mechanism in bovine granulosa cells is still unclear. Itaconic acid is an endogenous anti-inflammatory and antioxidant small-molecule compound that can alleviate ERS. Therefore, the aim of the current study is to evaluate the effect of ERS on necroptosis and investigate the ameliorative effect of itaconic acid against ERS-induced necroptosis in granulosa cells. Bovine granulosa cells were treated with tunicamycin (Tm) to induce ERS. After the addition of the necroptosis inhibitor Nec-1 and the detection of the necroptosis inducer acetylcholinesterase (AChE), flow cytometry, transmission electron microscopy, and mass spectrometry were used to analyze the expression of itaconic acid and IRG1 in the granulosa cells. In addition, the role of the PERK pathway downstream of ERS in ERS-induced necroptosis was also investigated. We report here that ERS can induce necroptosis in granulosa cells. Itaconic acid supplementation significantly attenuates the effect of ERS-induced damage. In summary, this research provides a scientific basis and a drug reference for treating follicular atresia and improving bovine reproductive capacity. |
| format | Article |
| id | doaj-art-5d6fe7236d3349d1814bd0cb428fae89 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-5d6fe7236d3349d1814bd0cb428fae892025-08-20T03:43:11ZengMDPI AGCells2073-44092025-03-0114641910.3390/cells14060419Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in BovineXiaorui Yang0Yue Chen1Xinzi Wang2Gaoqing Xu3Hongjie Wang4Xinqi Shu5He Ding6Xin Ma7Jing Guo8Jun Wang9Jing Zhao10Yi Fang11Hongyu Liu12Wenfa Lu13Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaKey Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, ChinaThe necroptosis of granulosa cells has been proven to be one of the important triggers of follicular atresia, which is an important cause of reduced reproductive capacity in cows. The rapid growth of granulosa cells is accompanied by endoplasmic reticulum stress (ERS), leading to granulosa cell death. However, the link between ERS and necroptosis, as well as its mechanism in bovine granulosa cells is still unclear. Itaconic acid is an endogenous anti-inflammatory and antioxidant small-molecule compound that can alleviate ERS. Therefore, the aim of the current study is to evaluate the effect of ERS on necroptosis and investigate the ameliorative effect of itaconic acid against ERS-induced necroptosis in granulosa cells. Bovine granulosa cells were treated with tunicamycin (Tm) to induce ERS. After the addition of the necroptosis inhibitor Nec-1 and the detection of the necroptosis inducer acetylcholinesterase (AChE), flow cytometry, transmission electron microscopy, and mass spectrometry were used to analyze the expression of itaconic acid and IRG1 in the granulosa cells. In addition, the role of the PERK pathway downstream of ERS in ERS-induced necroptosis was also investigated. We report here that ERS can induce necroptosis in granulosa cells. Itaconic acid supplementation significantly attenuates the effect of ERS-induced damage. In summary, this research provides a scientific basis and a drug reference for treating follicular atresia and improving bovine reproductive capacity.https://www.mdpi.com/2073-4409/14/6/419itaconic acidERSgranulosa cellsnecroptosis |
| spellingShingle | Xiaorui Yang Yue Chen Xinzi Wang Gaoqing Xu Hongjie Wang Xinqi Shu He Ding Xin Ma Jing Guo Jun Wang Jing Zhao Yi Fang Hongyu Liu Wenfa Lu Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine Cells itaconic acid ERS granulosa cells necroptosis |
| title | Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine |
| title_full | Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine |
| title_fullStr | Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine |
| title_full_unstemmed | Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine |
| title_short | Ameliorative Effect of Itaconic Acid/IRG1 Against Endoplasmic Reticulum Stress-Induced Necroptosis in Granulosa Cells via PERK-ATF4-AChE Pathway in Bovine |
| title_sort | ameliorative effect of itaconic acid irg1 against endoplasmic reticulum stress induced necroptosis in granulosa cells via perk atf4 ache pathway in bovine |
| topic | itaconic acid ERS granulosa cells necroptosis |
| url | https://www.mdpi.com/2073-4409/14/6/419 |
| work_keys_str_mv | AT xiaoruiyang ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT yuechen ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT xinziwang ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT gaoqingxu ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT hongjiewang ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT xinqishu ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT heding ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT xinma ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT jingguo ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT junwang ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT jingzhao ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT yifang ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT hongyuliu ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine AT wenfalu ameliorativeeffectofitaconicacidirg1againstendoplasmicreticulumstressinducednecroptosisingranulosacellsviaperkatf4achepathwayinbovine |