title: NDRG2 is a novel p53-associated regulator of apoptosis in C6-originated astrocytes exposed to oxygen-glucose deprivation.
abstract: N-myc downstream-regulated gene 2 (NDRG2) has been documented to be a pro-differentiative and anti-proliferative gene in cancer research. Our previous study found a significant NDRG2 up-regulation in reactive astrocytes of penumbra after transient focal cerebral ischemia, which was parallel to the enhancement of TUNEL-positive signals. However, it is still uncertain whether NDRG2 participates in cellular apoptosis induced by ischemia-reperfusion injury in brain. In this study, we investigated the role of NDRG2 in cellular apoptosis induced by oxygen-glucose deprivation (OGD) in IL-6-differentiated C6 glioma cells. The results showed that NDRG2 was up-regulated and translocated from the cytoplasm to the nucleus after OGD exposure. NDRG2 over-expression exhibited an anti-proliferative effect and increased the Bax/Bcl-2 ratio after OGD exposure, while NDRG2 silencing promoted the cellular proliferation and attenuated the up-regulation of Bax/Bcl-2 ratio. The pro-apoptotic effect of p53 was verified by the results in which p53 silencing greatly reduced the percentage of OGD-induced apoptotic cells. p53 silencing also reduced the OGD-induced NDRG2 up-regulation. However, over-expression of p53 did not further improve the NDRG2 up-regulation. In conclusion, NDRG2 is a p53-associated regulator of apoptosis in C6-originated astrocytes after OGD exposure. These findings bring insight to the roles of NDRG2 in ischemic-hypoxic injury and provide potential targets for future clinical therapies on stroke.
authors: Department of Anesthesiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors: Yan
authors: Y
authors: Li
authors: Ning
authors: N
authors: Xu
authors: Lei
authors: L
authors: Cai
authors: Zijun
authors: Z
authors: Gao
authors: Lan
authors: L
authors: Shen
authors: Qiaomei
authors: Q
authors: Zhang
authors: Wugang
authors: W
authors: Hou
authors: Haixing
authors: H
authors: Zhong
authors: Qiang
authors: Q
authors: Wang
authors: Lize
authors: L
authors: Xiong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C466228:NDRG2 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005947:Glucose; D010100:Oxygen