The Study On The Expression And Function Of Neuroglobin

Neuroglobin is an endogenous neuroprotective molecule,which can protect neurons from hypoxia/ischemia,oxidative stress and beta-amyloid-induced neuron injury.Stroke and neurodegenerative disorders can activate the endogenous neuroprotection mechanism,so making use of this mechanism may lead to the development of new approaches for the treatment of sroke and neurodegenerative disorders.Therefore,the drugs capable of up-regulating endogenous Ngb have great potential in the prevention and treatment of stroke and other neurological diseases.Earlier studies have shown that valproic acid plays a protective role in neuron injury induced by many factors,in other words,VPA has an ability of protecting the brain from neural damage induced by stroke and related diseases of the nervous system.Formononetin can protect neurons against oxidative stress and neurotoxicity induced by L-glutamate or beta-amyloid.These results suggest that VPA and formononetin may act as neuroprotective drugs.However,the neroprotection mechanisms of VPA and formononetin have yet to be further studied.Through Western blot,real-time quantitative PCR and luciferase assay,we found that VPA and formononetin treatments markedly increased the protein levels,mRNA levels and promoter activity of Ngb in mouse N2a cells and human SKNSH cells.Transcription factor CREB mediated VPA and formononetin-induced Ngb up-regulation.CREB specific inhibitor KG501 or CREB dominant negative mutant KCREB attenuated VPA and formononetin-induced Ngb promoter activity.The MTT assay showed that VPA could protect N2a cell from H2O2-induced neurotoxicity.Furthermore,CRE2 site mediated formononetin-induced upregulation of mouse Ngb promoter activity.In brief,our data showed that,CREB mediates VPA and formononetin-induced Ngb up-regulation,which may contribute to the neuroprotective effects of VPA and formononetin in neurons.