Propofol Induces the Expression of Nrf2 and HO-1 in Echinococcus granulosus via the JNK and p38 Pathway In Vitro

Tropical Medicine and Infectious Disease

article

Guangyi Luo¹  Bin Ma³  Yufeng Jiang⁴  Hailong Lv² 

[1] Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu;Section for Hepatopancreatobiliary Surgery, Department of General Surgery, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu;Department of General Surgery, Jinxiang People’s Hospital;School of Basic Medicine, Chengdu Medical College

关键词: Echinococcus granulosus;    protoscoleces;    MAPK;    Nrf2;    propofol;   

DOI  :  10.3390/tropicalmed8060306

学科分类：社会科学、人文和艺术（综合）

来源: mdpi

【 摘 要 】

The purpose of this study was to establish the relationship between mitogen-activated protein kinase (MAPK) and Nrf2 signaling pathways in Echinococcus granulosus (E. granulosus). E. granulosus protoscoleces (PSCs) cultured in vitro were divided into different groups: a control group, PSCs were pretreated with various concentrations of propofol followed by exposure to hydrogen peroxide (H2O2), and PSCs were pretreated with MAPK inhibitors, then co-treated with propofol and incubated in the presence of H2O2. PSCs activity was observed under an inverted microscope and survival rate was calculated. Reactive oxygen species (ROS) was detected by fluorescence microscopy, western blotting was used to detect the expression of Nrf2, Bcl-2, and heme oxygenase 1 (HO-1) in the PSCs among different groups. Pretreatment of PSCs with 0–1 mM propofol for 8 h prevented PSCs death after exposure to 0.5 mM H2O2. PSCs were pretreated with PD98059, SB202190, or SP600125 for 2 h, co-treated with propofol for an additional 8 h, and then exposed to 0.5 mM H2O2 for 6 h. On day 6, the PSCs viability was 42% and 39% in the p38 and JNK inhibitor groups, respectively. Additionally, pretreatment with propofol significantly attenuated the generation of ROS following H2O2 treatment. Propofol increased the expression of Nrf2, HO-1, and BCL2 compared with that of the control group. Pretreatment PSCs with SP600125 or SB202190, co-incubation with propofol and H2O2, can reduce the expression of Nrf2, HO-1, and BCL2 (p < 0.05). These results suggest that propofol induces an upregulated expression of HO-1 and Nrf2 by activation of the JNK and p38 MAPK signaling pathways. This study highlights the cross role of metabolic regulation of ROS signaling and targeting signalling pathways that may provide a promising strategy for the treatment of E. granulosus disease.

【 授权许可】

CC BY