The nuclear factor E2-related factor 2 participates in morphine-induced autophagy

Abstract

Abstract Morphine is an important potent analgesic which has many side effects such as addiction. Studies have demonstrated that autophagy play an important role during morphine addiction especially in morphine withdrawal. However, the molecular basis of morphine-induced autophagy has been not fully elucidated. The nuclear factor E2-related factor 2 (NRF2) is a well-known transcription factor that plays a critical role in antioxidation and even autophagy, furthermore, previous study showed that it increased in the frontal cortex and striatum of the mice which suffering from morphine withdrawal, indicating that NRF2 may involve in morphine addiction. In the present study, we aim to clarify the role of NRF2 in morphine-induced autophagy in vitro. Our results showed morphine could significantly increase the expression of NRF2 and further induce autophagy in SH-SY5Y cells. In addition, pretreatment of NRF2 inhibitor could reverse the upregulation of NRF2 and autophagy after morphine administration, indicating NRF2 play a key role in morphine-induced autophagy. Interestingly, we found NRF2 was also regulated by autophagy because pretreated with 3-Methyladenine after morphine administration significantly increased the expression of NRF2. In conclusion, our study revealed a critical role of NRF2 in morphine-induced autophagy and the feedback effect of autophagy on NRF2.