Remifentanil induces autophagy and prevents hydrogen peroxide-induced apoptosis in Cos-7 cells

  • Yoon, Ji-Young (Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital) ;
  • Baek, Chul-Woo (Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital) ;
  • Woo, Mi-Na (Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital) ;
  • Kim, Eun-Jung (Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital) ;
  • Yoon, Ji-Uk (Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital) ;
  • Park, Chang-Hoon (Department of Dental Anesthesia and Pain Medicine, Pusan National University Dental Hospital)
  • Received : 2016.08.16
  • Accepted : 2016.09.02
  • Published : 2016.09.30


Background: This study investigated the effect of remifentanil pretreatment on Cos-7 cells exposed to oxidative stress, and the influence of remifentanil on intracellular autophagy and apoptotic cell death. Methods: Cells were divided into 4 groups: (1) Control: non-pretreated cells were incubated in normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$). (2) $H_2O_2$: non-pretreated cells were exposed to $H_2O_2$ for 24 h. (3) RPC+$H_2O_2$: cells pretreated with remifentanil were exposed to $H_2O_2$ for 24 h. (4) 3-MA+RPC+$H_2O_2$: cells pretreated with 3-Methyladenine (3-MA) and remifentanil were exposed to $H_2O_2$ for 24 h. We determined the cell viability of each group using an MTT assay. Hoechst staining and FACS analysis of Cos-7 cells were performed to observe the effect of remifentanil on apoptosis. Autophagy activation was determined by fluorescence microscopy, MDC staining, and AO staining. The expression of autophagy-related proteins was observed using western blotting. Results: Remifentanil pretreatment increased the viability of Cos-7 cells exposed to oxidative stress. Hoechst staining and FACS analysis revealed that oxidative stress-dependent apoptosis was suppressed by the pretreatment. Additionally, fluorescence microscopy showed that remifentanil pretreatment led to autophagy-induction in Cos-7 cells, and the expression of autophagy-related proteins was increased in the RPC+$H_2O_2$ group. Conclusions: The study showed that remifentanil pretreatment stimulated autophagy and increased viability in an oxidative stress model of Cos-7 cells. Therefore, we suggest that apoptosis was activated upon oxidative stress, and remifentanil preconditioning increased the survival rate of the cells by activating autophagy.



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