title: The protection of acetylcholinesterase inhibitor on β-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells.
abstract: Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA's effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Jiao-Ning
authors.initials: JN
authors.lastname: Shen
authors.forename: Deng-Shun
authors.initials: DS
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
chemical_list: D000110:Acetylcholinesterase; D000470:Alkaloids; D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D012717:Sesquiterpenes; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C107953:RAC1 protein, human; C074636:amyloid beta-protein (25-35); C050426:huperzine A; C548244:ACHE protein, human; C548246:Ache protein, rat
keywords: acetylcholinesterase inhibitor; axon guidance; huperzine A; neurite outgrowth; β-amyloid