Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8478345 | Molecular and Cellular Neuroscience | 2018 | 45 Pages |
Abstract
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.
Keywords
IKKACMiNOSPFAhSOD1EAATsNSC34 cellsCBPSOD1GLTsMNsTDP-43dl-3-n-ButylphthalideICAMAEG-1Dulbecco Modified Eagle MediumSALSYY1NF-κBLPSDMEMCOX-2FBSPVDFGFAPsporadic ALSDMSOIκB kinaseRNA interferenceRNAiAstrocytesexcitatory amino acidamyotrophic lateral sclerosisamyotrophic lateral sclerosis (ALS)interleukinswithaferin AALSParkinson's diseaseNeurodegenerationtumor necrosis factor-αglutamate transportersHADHIV-associated dementiaDimethyl sulfoxidefetal bovine seruminducible nitric oxide synthasesuperoxide dismutase 1Cyclooxygenase-2TNF-αnuclear factor κBlipopolysaccharideastrocyte-conditioned mediumNF-κB pathwayintercellular adhesion moleculemotor neuronspolymerase chain reactionPCRparaformaldehydeCREB-binding proteinGlial fibrillary acidic proteintar DNA-binding protein 43polyvinylidenedifluorideastrocyte elevated gene-1Yin Yang 1
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Authors
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng,