Tumor grade related expression of neuroglobin is negatively regulated by PPARγ and confers antioxidant activity in glioma progression

Abstract Neuroglobin (NGB), distributed mainly in central and peripheral nervous systems, is a nerve globin with neuroprotective effects against oxidative stress resulting from hypoxia and ischemia. Recent studies have indicated that the expression of NGB is related to neurodegenerative disorders and cancers, but the molecular mechanisms for its transcriptional regulation and protection are not well defined. Here, we report that the expression of NGB in glioma is grade related and is negatively regulated by PPARγ. Specific PPARγ agonist reduces the expression of NGB, while its inhibitor enhances the expression. Moreover, NGB participates in regulating the phosphorylation of AKT in glioma cells, which may contribute to the glioma progression where accumulating oxidative pressure presents. Overexpression of NGB could protect glioma cells against 4-HNE induced cell death, and partially reverse PPARγ’s pro-apoptotic and anti-proliferative abilities. These results display an important role of NGB in glioma progression and a mechanism for its transcriptional regulation, and suggest that the treatment on glioma through PPARγ agonist appears to be triggered by the modulation of NGB.