title: Genistein Inhibits Aβ25-35-Induced Synaptic Toxicity and Regulates CaMKII/CREB Pathway in SH-SY5Y Cells.
abstract: Genistein (Gen), as a functional food in human diet, has shown many beneficial effects on neurodegenerative diseases such as Alzheimer's disease (AD). But the neuroprotective mechanism of Gen is not clear. Because synaptic failure is considered as the earliest phase in the pathogenesis of AD, we try to validate our hypothesis that synapse may be one target of Gen on protecting neurons. In this study, SH-SY5Y cells were pre-incubated with or without Gen for 2 h followed by the incubation with Aβ25-35 (25 μmol/L) for another 24 h. Flow cytometry, Western Blots, and RT-PCR analysis were used to test the synaptic factors. The data showed that Gen pre-treatment could reverse the Aβ25-35-induced down-regulation of synaptophysin and postsynaptic marker postsynaptic density-95. In addition, the down-regulation of NR1 and NR2B induced by Aβ25-35 which are subunits of N-methyl-D-aspartate receptor also could be antagonized by pre-treatment of Gen. Moreover, the factors of CaMKII/CREB signaling pathway were detected. The results showed that mRNA and protein expressions of (Ca(2+))/calmodulin(CaM), CaMKII/pCaMKII, and CREB/pCREB were significantly down-regulated by Aβ25-35, but they were all restored by the pre-treatment of Gen. Furthermore, Gen also maintained the intracellular Ca(2+) concentration which was disturbed by Aβ25-35. In conclusion, these results suggested that Gen could protect synaptic dysfunction induced by Aβ, and the mechanism might be associated with the regulation of synaptic markers and Ca(2+) level through activating CaM/CaMK/CREB signaling pathway.
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Yuan-Di
authors.initials: YD
authors.lastname: Xi
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Dan-Di
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Ningxia Key Laboratory of Cerebrocranial Diseases, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Huan-Ling
authors.initials: HL
authors.lastname: Yu
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Lin-Hong
authors.initials: LH
authors.lastname: Yuan
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Ma
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Public Health, Capital Medical University and Beijing Key Laboratory of Environmental Toxicology, No. 10 Xitoutiao, You An Men Wai, Beijing, 100069, China. xiaor22@ccmu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; C074636:amyloid beta-protein (25-35); D019833:Genistein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CREB; Calcium; Genistein; Neuroprotection; Synaptic plasticity; Synaptophysin