Sestrin2 protects against bavachin induced ER stress through AMPK/mTORC1 signaling pathway in HepG2 cells

Journal of Pharmacological Sciences

Yue Gao¹  Qingquan Liu²  Ying Yang²  Zheng Fan²  Guiming Guo²  Wei Zhou³  Yunxuan Ge³ 

[1] Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China;Department of Clinical Pharmacy, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China;Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China;

关键词: Bavachin;    Acute liver injury;    Sestrin2;    ER stress;   

DOI  :  

来源: DOAJ

【 摘 要 】

Bavachin (BV), a natural flavonoid compound derived from Psoralea corylifolia L, has been reported to be a potential hepatotoxin. Our previous studies have found that BV can induce endoplasmic reticulum (ER) stress-related cell apoptosis, but the molecular mechanism underlying BV-induced ER stress remains obscure. Sestrin2, a highly conserved stress-inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation. However, whether Sestrin2 participated in the ER stress related hepatotoxicity against BV is still elusive. In the present study, we aim to investigate the role of BV on liver injury of mice and the impact of Sestrin2 on BV-induced ER stress in HepG2 cells. The results in mice showed that BV induced ER stress related liver injury with increased Sestrin2 expression involvement. Knockdown of Sestrin2 with siRNA aggravated BV-induced ER stress significantly in HepG2 cells. Further mechanistic study uncovered that inhibition of mTORC1 with rapamycin blocked BV-induced ER stress, and treatment with Sestrin2 siRNA blocked the inhibition effect of AMPK to mTORC1. Therefore, constant mTORC1 would lead to accumulation of misfolded or unfolded proteins and aggravated ER stress. Collectively, our study indicates that Sestrin2 confers protection against BV-induced ER stress via activating of the AMPK/mTORC1 pathway.

【 授权许可】

Unknown