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  • Upregulation Sestrin2 protects against hydrogen peroxide-induced oxidative damage bovine mammary epithelial cells via a Keap1-Nrf2/ARE pathway.

Upregulation Sestrin2 protects against hydrogen peroxide-induced oxidative damage bovine mammary epithelial cells via a Keap1-Nrf2/ARE pathway.

Journal of cellular physiology (2020-06-11)
Mengjiao Chen, Yumeng Xi, Kunlin Chen, Peng Xiao, Shujie Li, Xiaochun Sun, Zhaoyu Han
초록

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.

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Sigma-Aldrich
DL-Glyceraldehyde 3-phosphate solution, 45-55 mg/mL in H2O
Sigma-Aldrich
MISSION® esiRNA, targeting human SESN2