{"title":"Sestrin 2 通过调节 mTOR/Nrf2 通路，保护人类晶状体上皮细胞免受过氧化氢诱导的氧化应激和细胞凋亡。","authors":"Xiao Tian, Jie Wei","doi":"10.1177/03946320241234741","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>We aimed to explore the effect and potential mechanism of Sestrin 2 (SESN2) in human lens epithelial cells (HLECs).</p><p><strong>Methods: </strong>To mimic the oxidative stress environment, SAR01/04 cells were treated with 200 μM hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) for 24 h. Cell viability and apoptosis were checked by cell counting kit-8 and flow cytometry. Western blot was taken to check the protein changes of SESN2, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, ribosomal protein S6 kinase B1 (p70S6K), p-p70S6K, and nuclear factor erythroid 2-related factor 2 (Nrf2). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected via the corresponding reagent kit. The levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>SESN2 was down-regulated in cataract lens tissue and up-regulated in SAR01/04 cells treated with H<sub>2</sub>O<sub>2</sub>. Under treatment of H<sub>2</sub>O<sub>2</sub>, up-regulation of SESN2 improved cell viability, enhanced the activity of SOD and CAT, inhibited cell apoptosis, and reduced the levels of MDA, ROS, IL-1β, IL-18, and TNF-α, while down-regulation of SESN2 caused the contrary effects. Further bioinformatics analysis suggested that SESN2 regulated the mTOR signaling pathway. Treatment of H<sub>2</sub>O<sub>2</sub> inhibited p-mTOR and p-p70S6K protein expression, while overexpression of SESN2 increased p-mTOR and p-p70S6K protein expression in the H<sub>2</sub>O<sub>2</sub> group and down-regulation of SESN2 further decreased p-mTOR and p-p70S6K protein expression in the H<sub>2</sub>O<sub>2</sub> group. Additionally, H<sub>2</sub>O<sub>2</sub> increased Nrf2 protein expression, and overexpression of SESN2 further increased Nrf2 protein expression in the H<sub>2</sub>O<sub>2</sub> group. Importantly, rapamycin (an inhibitor of mTOR signaling pathway) and knockdown of Nrf2 reversed the promotive effects of SESN2 on cell viability and the inhibitive effects of SESN2 on cell apoptosis, oxidative stress, and inflammatory reaction.</p><p><strong>Conclusion: </strong>SESN2 protected HLECs damage induced by H<sub>2</sub>O<sub>2</sub>, which was related to the activation of mTOR/Nrf2 pathway.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"38 ","pages":"3946320241234741"},"PeriodicalIF":3.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880533/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway.\",\"authors\":\"Xiao Tian, Jie Wei\",\"doi\":\"10.1177/03946320241234741\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>We aimed to explore the effect and potential mechanism of Sestrin 2 (SESN2) in human lens epithelial cells (HLECs).</p><p><strong>Methods: </strong>To mimic the oxidative stress environment, SAR01/04 cells were treated with 200 μM hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) for 24 h. Cell viability and apoptosis were checked by cell counting kit-8 and flow cytometry. Western blot was taken to check the protein changes of SESN2, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, ribosomal protein S6 kinase B1 (p70S6K), p-p70S6K, and nuclear factor erythroid 2-related factor 2 (Nrf2). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected via the corresponding reagent kit. The levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>SESN2 was down-regulated in cataract lens tissue and up-regulated in SAR01/04 cells treated with H<sub>2</sub>O<sub>2</sub>. Under treatment of H<sub>2</sub>O<sub>2</sub>, up-regulation of SESN2 improved cell viability, enhanced the activity of SOD and CAT, inhibited cell apoptosis, and reduced the levels of MDA, ROS, IL-1β, IL-18, and TNF-α, while down-regulation of SESN2 caused the contrary effects. Further bioinformatics analysis suggested that SESN2 regulated the mTOR signaling pathway. Treatment of H<sub>2</sub>O<sub>2</sub> inhibited p-mTOR and p-p70S6K protein expression, while overexpression of SESN2 increased p-mTOR and p-p70S6K protein expression in the H<sub>2</sub>O<sub>2</sub> group and down-regulation of SESN2 further decreased p-mTOR and p-p70S6K protein expression in the H<sub>2</sub>O<sub>2</sub> group. Additionally, H<sub>2</sub>O<sub>2</sub> increased Nrf2 protein expression, and overexpression of SESN2 further increased Nrf2 protein expression in the H<sub>2</sub>O<sub>2</sub> group. Importantly, rapamycin (an inhibitor of mTOR signaling pathway) and knockdown of Nrf2 reversed the promotive effects of SESN2 on cell viability and the inhibitive effects of SESN2 on cell apoptosis, oxidative stress, and inflammatory reaction.</p><p><strong>Conclusion: </strong>SESN2 protected HLECs damage induced by H<sub>2</sub>O<sub>2</sub>, which was related to the activation of mTOR/Nrf2 pathway.</p>\",\"PeriodicalId\":48647,\"journal\":{\"name\":\"International Journal of Immunopathology and Pharmacology\",\"volume\":\"38 \",\"pages\":\"3946320241234741\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880533/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Immunopathology and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/03946320241234741\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Immunopathology and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/03946320241234741","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Sestrin 2 protects human lens epithelial cells from oxidative stress and apoptosis induced by hydrogen peroxide by regulating the mTOR/Nrf2 pathway.
Objective: We aimed to explore the effect and potential mechanism of Sestrin 2 (SESN2) in human lens epithelial cells (HLECs).
Methods: To mimic the oxidative stress environment, SAR01/04 cells were treated with 200 μM hydrogen peroxide (H2O2) for 24 h. Cell viability and apoptosis were checked by cell counting kit-8 and flow cytometry. Western blot was taken to check the protein changes of SESN2, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, ribosomal protein S6 kinase B1 (p70S6K), p-p70S6K, and nuclear factor erythroid 2-related factor 2 (Nrf2). Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected via the corresponding reagent kit. The levels of interleukin (IL)-1β, IL-18, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay.
Results: SESN2 was down-regulated in cataract lens tissue and up-regulated in SAR01/04 cells treated with H2O2. Under treatment of H2O2, up-regulation of SESN2 improved cell viability, enhanced the activity of SOD and CAT, inhibited cell apoptosis, and reduced the levels of MDA, ROS, IL-1β, IL-18, and TNF-α, while down-regulation of SESN2 caused the contrary effects. Further bioinformatics analysis suggested that SESN2 regulated the mTOR signaling pathway. Treatment of H2O2 inhibited p-mTOR and p-p70S6K protein expression, while overexpression of SESN2 increased p-mTOR and p-p70S6K protein expression in the H2O2 group and down-regulation of SESN2 further decreased p-mTOR and p-p70S6K protein expression in the H2O2 group. Additionally, H2O2 increased Nrf2 protein expression, and overexpression of SESN2 further increased Nrf2 protein expression in the H2O2 group. Importantly, rapamycin (an inhibitor of mTOR signaling pathway) and knockdown of Nrf2 reversed the promotive effects of SESN2 on cell viability and the inhibitive effects of SESN2 on cell apoptosis, oxidative stress, and inflammatory reaction.
Conclusion: SESN2 protected HLECs damage induced by H2O2, which was related to the activation of mTOR/Nrf2 pathway.
期刊介绍：
International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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