Effect of oxidative stress in SH-SY5Y cell injury induced by deguelin / 中国药理学通报

ABSTRACT

Aim To study the correlation between oxidative stress and neurotoxicity induced by deguelin, providing the mechanism basis for the structural modification and drug combination about deguelin. Methods SH-SY5Y cells were exposed to deguelin ranging from 1. 56-100 jimol • L"1 for 24 to 72 h, whose survival rate was determined by CCK-8 assay. The content of LDH, MDA levels, GPx and antioidant enzyme activities of SOD were determined using the assay kits ac-cording the manufacturer's protocol. And the content of ROS was determined by flow cytometry. The expressions of MEK, EGF, ERK and CREB were determined by immunoblotting. Results Deguelin obviously inhibited the growth of SH-SY5Y cells in a concentra-tion-and time-dependent manner ( P < 0. 05 ). After the cells were injured by deguelin, the content of ROS, LDH and MDA in SH-SY5Y cells increased obviously (P <0. 05), while the vitality of GPx and SOD decreased obviously ( P < 0. 05) in a dose-dependent manner. Furthermore, the protein expression levels of MEK, EGF, RAS and CREB in MAPK/ERK signaling pathway decreased obviously when treated with deguelin in a dose-dependent manner. (P < 0. 05). Conclusions The trauma of SH-SY5Y cells induced by deguelin is closely related to oxidative stress, in which MAPK/ERK signaling pathway may play a mediating role.