Cu(Ⅱ) attenuates oligomeic and fibrillar A β-induced activation of BV-2 microglia cells
会议名称:《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期:2009年
学科分类:1002[医学-临床医学] 100203[医学-老年医学] 10[医学]
关 键 词:Alzheimer’s disease amyloid β-peptide copper nitric oxide(NO) TNFβ
摘 要:正Background Amyloid-β peptide(Aβ) is one of the main components of senile plaques,a pathological hallmark of Alzheimer’s disease(AD).Activated microglia represents a major source of inflammatory factors in Alzheimer’s disease and a possible source of cytotoxic factors.Aβpeptide has been shown to activate microglia and stimulate their production of inflammatory *** evidence has shown that the redox-active biometal Cu(Ⅱ) can modulate the physiochemical properties of Aβ.This article aims to evaluate the effect of oligomeric and fibrillar Aβand Cu(Ⅱ) on microglia activation. Methods Oligomeric and fibrilliar Aβwere prepared by incubation at 4℃for 24h or at 37℃for 7days,respectively.Aβpeptide assemblies were extensively characterized by CD,TH-T fluorescence and sedimentation *** the Aβ-Cu(Ⅱ) complex preparation,the above oligomeric and fibrillar Aβwere incubated with Cu(Ⅱ) for 1h to form the Aβ-Cu(Ⅱ) complexes, *** immortalized murine BV-2 cells were grown and maintained in Dulbecco’s Modified Eagles Medium (DMEM)(supplemented with 10%fetal bovine serum and 100 mg/mL streptomycin and 10 U/mL penicillin) at 37℃in a humidified incubator with 5%CO2.20μM concentration of oligomeric or fillbrillar Aβwas chosen,and LPS was chosen as positive control and PBS as vehicle *** viability was quantitively determined using the MTT *** BV-2 cells co-incubated with different forms of Aβor their Aβ-Cu(Ⅱ) complexes for 24 h,real-time PCR(RT-PCR) detected TNFαand iNOS mRNA expression levels of BV-2 *** production of nitric oxide(NO) was quantified by measuring the released NO metabolites(nitrate and nitrite) with Griess *** Cu(Ⅱ) has an important effect on the oligomeric and filbrillar Aβsecondary structure and aggregation,and will disrupts p-sheet structure and convertsβaggregates into non-β*** oligomeric and filbrillar Aβcan induce microglial activation,however the cellular signal ways are different due to t