Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY ...Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM 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 ! 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-SYSY 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 dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.展开更多
基金supported by a grant from the National Key Research and Development Plan of China,No.2016YFC1101500the National Natural Science Foundation of China,No.11672332,11102235,8167050417+1 种基金the Key Science and Technology Support Foundation of Tianjin City of China,No.17YFZCSY00620the Natural Science Foundation of Tianjin City of China,No.15JCYBJC28600,17JCZDJC35400
文摘Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson＇s disease. However, the mecha- nism underlying this action remains unknown. This study investigated human SH-SYSY cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed： a control group （without any treatment）, a genistein group （incubated with 20 μM genistein）, a rote- none group （treated with 50 μM rotenone）, and a rotenone ＋ genistein group （incubated with 20 μM genistein and then treated with 50μM 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 ! 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-SYSY 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 dis- ease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.
