dBET1降解溴结构域蛋白4抑制α突触核蛋白寡聚体的神经毒性作用研究  

Degradation of BRD4protein with dBET1inhibits neurotoxic effects ofα-synuclein oligomers

作　　者：郑银娟 张飘 黄沛婷 张玉虎 Zheng Yinjuan;Zhang Piao;Huang Peiting;Zhang Yuhu(School of Medicine,South China University of Technology,Guangzhou 510006,Guangdong Province,China)

机构地区：[1]华南理工大学医学院,广州510006 [2]广东省人民医院(广东省医学科学院)神经内科

出　　处：《中华老年心脑血管病杂志》2024年第5期573-577,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(82071419);“登峰计划”科研专项(DFJH201907)。

摘　　要：目的探究用dBET1降解溴结构域蛋白4(BRD4)能否抑制α突触核蛋白(α-syn)寡聚体导致的神经炎症及氧化应激。方法dBET1与α-syn寡聚体共同处理BV2细胞或SH-SY5Y细胞,分为对照组、α-syn组、α-syn+500 nmol/L dBET1组,α-syn+1000nmol/L dBET1组,1000nmol/L dBET1组。定量聚合酶链反应检测炎性因子及抗炎因子,蛋白质免疫印迹检测BRD4、核因子E2相关因子2(Nrf2)、磷酸化核转录因子κB(p-NF-κB)及磷酸化α-syn(p-α-synuclein)等。结果α-syn+1000nmol/L dBET1组炎性因子mRNA、BRD4、p-NF-κB、p-α-synuclein表达低于α-syn组,而抗炎因子mRNA、细胞核Nrf2表达显著高于α-syn组[(2.02±0.14)vs(0.96±0.24),P<0.05]。结论dBET1通过p-NF-κB及Nrf2在一定程度上能抑制α-syn导致的神经炎症及氧化应激等,为进一步运用于治疗帕金森病等疾病提供理论基础。Objective To investigate whether degradation of bromodomain-containing protein 4(BRD4)protein with dBET1can inhibit neuroinflammation and oxidative stress caused byα-synuclein(α-syn)oligomers.Methods After BV2cells or SH-SY5Ycells were treated with dBET1andα-syn oligomers,the cells were divided into Control group,α-syn group,α-syn+500 and 1000nmol/L dBET1groups,and dBET1group(1000nmol/L).Real-time quantitative fluorescent PCR(qPCR)was used to detect the expression of inflammatory factors and anti-inflammatory factors,and Western blotting was employed to measure the expression of BRD4,nuclear factor 2associated factor 2(Nrf2),phosphorylated nuclear transcription factor-κB(p-NF-κB)and phosphorylatedα-synuclein(p-α-synuclein).Results Theα-syn+1000nmol/L dBET1group had lower mRNA levels of inflammatory factors and reduced protein levels of BRD4,p-NF-κB and p-α-synuclein,but higher mRNA levels of anti-inflammatory factors and decreased Nrf2protein level(2.02±0.14 vs 0.96±0.24,P<0.05)when compared with theα-syn group.Conclusion dBET1can inhibit neuroinflammation and oxidative stress caused byα-synuclein through p-NF-κB and Nrf2to a certain extent,which further provides a theoretical basis for its application in the treatment of Parkinson's disease.

关 键 词：帕金森病 含溴结构域蛋白 突触核蛋白类 NF-E2相关因子2 氧化性应激 神经炎 dBET1 

分 类 号：R742.5[医药卫生—神经病学与精神病学]