Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant ?-synuclein.

ABSTRACT: Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of ?-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 ?M genistein), a rotenone group (treated with 50 ?M rotenone), and a rotenone + genistein group (incubated with 20 ?M genistein and then treated with 50 ?M rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.

SUBMITTER: Wu HC 

PROVIDER: S-EPMC6108222 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature