Upregulation Sestrin2 protects against hydrogen peroxide‐induced oxidative damage bovine mammary epithelial cells via a Keap1‐Nrf2/ARE pathway
| Autor: | Kun-Lin Chen, Mengjiao Chen, Peng Xiao, Zhaoyu Han, Yumeng Xi, Xiao-Chun Sun, Shujie Li |
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| Rok vydání: | 2020 |
| Předmět: |
Transcriptional Activation
0301 basic medicine NF-E2-Related Factor 2 Physiology Clinical Biochemistry Down-Regulation Apoptosis Mitochondrion medicine.disease_cause Antioxidants 03 medical and health sciences Mammary Glands Animal 0302 clinical medicine Downregulation and upregulation medicine Animals Cells Cultured Cell Proliferation chemistry.chemical_classification Reactive oxygen species Kelch-Like ECH-Associated Protein 1 Chemistry Autophagy Nuclear Proteins Epithelial Cells Hydrogen Peroxide Cell Biology KEAP1 Up-Regulation Cell biology Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis Cattle Signal transduction Reactive Oxygen Species Carboxylic Ester Hydrolases Oxidative stress Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 236:392-404 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | Sestrin2 (SESN2) is a highly conservative oxidative stress protein that can regulate energy metabolism, cell proliferation, apoptosis, and mitochondria autophagy processes. It plays a role as an antioxidant in various diseases. The aims of the present study were to explore the underlying role of SESN2 after hydrogen peroxide (H2 O2 ) treatment in bovine mammary epithelial cells (MAC-T cells) by the methods of knockout or overexpression of SESN2. The results show that knockout of Sestrin2 exacerbate apoptosis, upregulate the expressions of Bax/Bcl2 in H2 O2 -treated MAC-T cells. Moreover, knockout of SESN2 also promoted reactive oxygen species (ROS) generation and exacerbated oxidative damage in H2 O2 -treated MAC-T cells. On the contrary, overexpression of SESN2 decreased apoptosis by downregulation of Bax/Bcl2 level decreased ROS generation and blocked oxidative damage in H2 O2 -treated MAC-T cells. In addition, results indicate that the Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor (erythroid-derived 2) like2 (Nrf2)/antioxidant response element (ARE) signaling pathway was activated by H2 O2 ; upregulation of SESN2 could relieve oxidative stress by inducing the expression of Keap1, Nrf2, HO-1, and NDPH: quinone oxidoreductase-1 protein. In conclusion, this study demonstrates that expression of SESN2 was significantly increased after H2 O2 treatment and that SESN2 can alleviate oxidative stress and cell apoptosis in H2 O2 -treated MAC-T cells through activation of the Keap1-Nrf2/ARE pathway. |
| Databáze: | OpenAIRE |
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