Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein
Huan-Cheng Wu
Qun-Liang Hu
Shi-Jun Zhang
Yan-Min Wang
Zhan-Kui Jin
Ling-Fu Lv
Sai Zhang
Zhen-Lin Liu
Hong-Lian Wu
Ou-Mei Cheng
摘要：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 αt-synuclein.Four groups of cells were assayed:a control group (without any treatment),a genistein group (incubated with 20 μM genistein),a rotenone group (treated with 50 μM rotenone),and a rotenone + genistein group (incubated with 20 μM genistein and then treated with 50 μM 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 deoxymucleotidyl 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.
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资助基金：This study was supported by a grant from the National Key Research and Development Plan of China,(No.2016YFC1101500)the National Natural Science Foundation of China,(No.11672332,11102235,8167050417)the Key Science and Technology Support Foundation of Tianjin City of China,(No.17YFZCSY00620)the Natural Science Foundation of Tianjin City of China,(No.15JCYBJC28600,17JCZDJC35400)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 1375-1383 )
英文信息