中国药理学通报Issue(5):619-622,623,5.DOI:10.3969/j.issn.1001-1978.2014.05.007
丙戊酸通过CREB上调脑红蛋白并保护N2 a细胞免受双氧水诱导的神经损伤
Valproic acid induces neuroglobin protein by CREB and protects N2a cells against H2 O2-induced neurotoxicity
摘要
Abstract
Aim To investigate the effect and mecha-nism of valproic acid on neuroglobin expression, and the neuroprotective role of valproic acid against H2 O2-induced neurotoxicity. Methods Western blot, RT-PCR and luciferase assay were used to detect the pro-tein levels, mRNA levels and promoter activity of mouse and human neuroglobin induced by valproic acid. Luciferase assay was used to investigate the role of transcription factor CREB in the up-regulation of neuroglobin by valproic acid. MTT assay was used to evaluate the effect of valproic acid against H2 O2-in-duced neurotoxicity. Results VPA treatment marked-ly increased the protein levels, mRNA levels and pro-moter activity of Ngb in mouse N2 a cells and human SKNSH cells. CREB specific inhibitor KG501 or CREB dominant negative mutant KCREB attenuated VPA-induced Ngb promoter activity. VPA could pro-tect N2a cells from H2 O2-induced neurotoxicity. Con-clusion CREB mediates VPA-induced Ngb up-regula-tion, which may contribute to the neuroprotective effects of VPA in oxidative stress in neurons.关键词
丙戊酸/脑红蛋白/CREB/N2a/SKNSH/双氧水/神经损伤Key words
valproic acid/neuroglobin/CREB/N2 a/SKNSH/H2 O2/neurotoxicity分类
医药卫生引用本文复制引用
刘宁,寻禹,李亚丹,王婷婷,钟爱军,姚亮元,袁秀菊,向双林..丙戊酸通过CREB上调脑红蛋白并保护N2 a细胞免受双氧水诱导的神经损伤[J].中国药理学通报,2014,(5):619-622,623,5.基金项目
国家重点基础研究发展计划(973计划)资助项目( No 2010CB529900) (973计划)
湖南省教育厅重点项目(No 11A072) (No 11A072)
湖南省属科研机构技术创新发展专项(No 2010TF2014) (No 2010TF2014)
长沙市科技局重点项目(No K1205221-31) (No K1205221-31)