Zerumbone attenuates MPP+-induced cytotoxicity in human neuroblasto-ma SH-SY5Y cells by inhibition of oxidative stress / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of zerumbone ( ZER) in 1-methyl-4-phenylpyridinium ( MPP+)-in-duced cytotoxicity of human neuroblastoma SH-SY5Y cells. METHODS:Human neuroblastoma SH-SY5Y cells were cul-tured in vitro and the protective effect of ZER against MPP+-induced cytotoxicity was measured by CCK-8 assay. Flow cy-tometry was used to determine the apoptosis and reactive oxygen species (ROS). The expression of Parkinson disease pro-tein 7 (PARK7) was knocked-down by using PARK7-specific short hairpin RNA (shRNA). The protein levels of PARK7, nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by Western blot. RESULTS:MMP+remarkably reduced the cell viability in a dose-dependent and time-dependent manner. The SH-SY5Y cell injury model was established by treatment with MPP+ at 600 μmol/L for 24 h. ZER up-regulated the protein levels of PARK7 and Nrf2 (P<0.05), alleviated apoptosis (P<0.05), and reduced ROS production (P<0.05) in the SH-SY5Y cell injury model. Meanwhile, N-acetyl-L-cysteine (NAC) had the similar functions. Moreover, significant reductions in the protein levels of Nrf2 and HO-1 ( P<0.05), and obvious increases in apoptosis ( P<0.05) and ROS level ( P<0.05) were demonstrated in PARK7-knockdown cells. CONCLUSION:ZER protects SH-SY5Y cells against MPP+-induced cytotoxi-city, which may be related to activation of PARK7/Nrf2/HO-1 pathway, and subsequent attenuation of oxidative stress and apoptosis.