Tat-NOL3 protects against hippocampal neuronal cell death induced by oxidative stress through the regulation of apoptotic pathways

Sohn,Eun  Jeong; Shin,Min  Jea; Eum,Won  Sik; Kim,Dae  Won; Yong,Ji  In; Ryu,Eun  Ji; Park,Jung  Hwan; Cho,Su  Bin; Cha,Hyun  Ju; Kim,Sang  Jin; Yeo,Hyeon  Ji; Yeo,Eun  Ji; Choi,Yeon  Joo; Im,Seung  Kwon; Kweon,Hae  Young; Kim,Duk-Soo; Yu,Yeon  Hee; Cho,Sung-Woo; Park,Meeyoung; Park,Jinseu; Cho,Yong-Jun; Choi,Soo  Young

doi:10.3892/ijmm.2016.2596

Tat-NOL3 protects against hippocampal neuronal cell death induced by oxidative stress through the regulation of apoptotic pathways

Authors:
- Eun Jeong Sohn
- Min Jea Shin
- Won Sik Eum
- Dae Won Kim
- Ji In Yong
- Eun Ji Ryu
- Jung Hwan Park
- Su Bin Cho
- Hyun Ju Cha
- Sang Jin Kim
- Hyeon Ji Yeo
- Eun Ji Yeo
- Yeon Joo Choi
- Seung Kwon Im
- Hae Young Kweon
- Duk-Soo Kim
- Yeon Hee Yu
- Sung-Woo Cho
- Meeyoung Park
- Jinseu Park
- Yong-Jun Cho
- Soo Young Choi
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Affiliations: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon-do 24252, Republic of Korea, Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, Gangwon-do 25457, Republic of Korea, Department of Agricultural Biology, National Academy of Agricultural Sciences, RDA, Wanju-gun, Jeollabuk-do 55365, Republic of Korea, Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-si, Chungnam 31538, Republic of Korea, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea, Department of Neurosurgery, College of Medicine, Hallym University, Chuncheon, Gangwon-do 24253, Republic of Korea
Published online on: May 19, 2016 https://doi.org/10.3892/ijmm.2016.2596
Pages: 225-235

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Abstract

Oxidative stress-induced apoptosis is associated with neuronal cell death and ischemia. The NOL3 [nucleolar protein 3 (apoptosis repressor with CARD domain)] protein protects against oxidative stress-induced cell death. However, the protective mechanism responsible for this effect as well as the effects of NOL3 against oxidative stress in ischemia remain unclear. Thus, we examined the protective effects of NOL3 protein on hydrogen peroxide (H2O2)-induced oxidative stress and the mechanism responsible for these effects in hippocampal neuronal HT22 cells and in an animal model of forebrain ischemia using Tat-fused NOL3 protein (Tat-NOL3). Purified Tat-NOL3 protein transduced into the H2O2-exposed HT22 cells and inhibited the production of reactive oxygen species (ROS), DNA fragmentation and reduced mitochondrial membrane potential (ΔΨm). In addition, Tat-NOL3 prevented neuronal cell death through the regulation of apoptotic signaling pathways including Bax, Bcl-2, caspase-2, -3 and -8, PARP and p53. In addition, Tat-NOL3 protein transduced into the animal brains and significantly protected against neuronal cell death in the CA1 region of the hippocampus by regulating the activation of microglia and astrocytes. Taken together, these findings demonstrate that Tat-NOL3 protein protects against oxidative stress-induced neuronal cell death by regulating oxidative stress and by acting as an anti-apoptotic protein. Thus, we suggest that Tat-NOL3 represents a potential therapeutic agent for protection against ischemic brain injury.

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