Valproic acid induces neuroglobin protein by CREB and protects N2a cells against H2 O2-induced neurotoxicity / 中国药理学通报

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.