Upregulation Sestrin2 protects against hydrogen peroxide‐induced oxidative damage bovine mammary epithelial cells via a Keap1‐Nrf2/ARE pathway
Mengjiao Chen, Yumeng Xi, Kunlin Chen, Peng Xiao, Shujie Li, Xiaochun Sun, Zhaoyu Han
Abstract
Abstract 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 (H 2 O 2 ) 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 H 2 O 2 ‐treated MAC‐T cells. Moreover, knockout of SESN2 also promoted reactive oxygen species (ROS) generation and exacerbated oxidative damage in H 2 O 2 ‐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 H 2 O 2 ‐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 H 2 O 2 ; 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 H 2 O 2 treatment and that SESN2 can alleviate oxidative stress and cell apoptosis in H 2 O 2 ‐treated MAC‐T cells through activation of the Keap1‐Nrf2/ARE pathway.