Tat-NOL3 protects against hippocampal neuronal cell death induced by oxidative stress through the regulation of apoptotic pathways
| Autor: | Hyeon Ji Yeo, Hae Young Kweon, Sung-Woo Cho, Yong-Jun Cho, Jinseu Park, Duk-Soo Kim, Hyun Ju Cha, Seung Kwon Im, Meeyoung Park, Eun Ji Yeo, Jung Hwan Park, Sang Jin Kim, Su Bin Cho, Ji In Yong, Eun Jeong Sohn, Min Jea Shin, Won Sik Eum, Eun Ji Ryu, Yeon Joo Choi, Soo Young Choi, Dae Won Kim, Yeon Hee Yu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell Survival Recombinant Fusion Proteins Muscle Proteins Apoptosis DNA Fragmentation Mitochondrion Biology medicine.disease_cause Neuroprotection Hippocampus Brain Ischemia Cell Line 03 medical and health sciences Mice Transduction Genetic Genetics medicine Animals Humans Membrane Potential Mitochondrial Neurons 030102 biochemistry & molecular biology General Medicine Cell Cycle Checkpoints Cell cycle Cell biology Mitochondria Disease Models Animal Oxidative Stress 030104 developmental biology Neuroprotective Agents CARD domain tat Gene Products Human Immunodeficiency Virus Signal transduction Apoptosis Regulatory Proteins Gerbillinae Reactive Oxygen Species Oxidative stress Signal Transduction |
| Zdroj: | International journal of molecular medicine. 38(1) |
| ISSN: | 1791-244X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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