Chunni Cao1, Yanxiang Zhang2, Zuofu Zhang3, Qi Chen2. 1. Department of Hyperbaric Oxygen Therapy, Yantai Yuhuangding Hospital , Yantai , China. 2. Department of Neurology, Yantai Yuhuangding Hospital , Yantai , China. 3. Department of Joint Orthopedics, Yantai Yuhuangding Hospital , Yantai , China.
Abstract
Background: Ketamine (KET) is known to be used in pediatric anaesthetic, whereas many evidences revealed that KET generated neurotoxicity. In our study, we found KET decreased the level of LncRNA taurine-upregulated gene 1 (TUG1). Hence, the aim of our study is to investigate whether small interfering TUG1 (siTUG1) has effect on KET-induced rat hippocampal neurons. Material and methods: siTUG1 and KET alone or in combination was used to treat with neurons for 12 h. MTT assays was used to detect hippocampal neurons viability. Cell apoptosis and reactive oxygen species (ROS) level were analysed by flow cytometry assay. TUG1 level was determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. The levels of Bax, Bcl-2, cleaved-caspase-3, p38 and p-p38 were measured by western blot (WB) assay. Results: Neurons treated by siTUG1 and KET had a higher optical density (OD) value, a lower apoptosis rate and lower ROS level. Neurons treated by the combination of siTUG1 and KET had lower levels of TUG1, cleaved-caspase-3 and p-p38 than those under KET treatment. Besides, siTUG1 + KET group (siTUG1 and KET treated neurons) had a higher Bcl-2 level than KET group. Conclusion: We found that siTUG1 decreased KET-induced hippocampal neurons apoptosis and ROS level, and increased hippocampal neurons viability. siTUG1 decreased neurons apoptosis via signaling pathways of Bax/Bcl-2 and Caspases, and increased neurons viability by signaling pathway of p38 MAPK. Our results indicate that KET-induced neurotoxicity might be reduced by inhibiting TUG1.
Background: Ketamine (KET) is known to be used in pediatric anaesthetic, whereas many evidences revealed that KET generated neurotoxicity. In our study, we found KET decreased the level of LncRNA taurine-upregulated gene 1 (TUG1). Hence, the aim of our study is to investigate whether small interfering TUG1 (siTUG1) has effect on KET-induced rat hippocampal neurons. Material and methods: siTUG1 and KET alone or in combination was used to treat with neurons for 12 h. MTT assays was used to detect hippocampal neurons viability. Cell apoptosis and reactive oxygen species (ROS) level were analysed by flow cytometry assay. TUG1 level was determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. The levels of Bax, Bcl-2, cleaved-caspase-3, p38 and p-p38 were measured by western blot (WB) assay. Results: Neurons treated by siTUG1 and KET had a higher optical density (OD) value, a lower apoptosis rate and lower ROS level. Neurons treated by the combination of siTUG1 and KET had lower levels of TUG1, cleaved-caspase-3 and p-p38 than those under KET treatment. Besides, siTUG1 + KET group (siTUG1 and KET treated neurons) had a higher Bcl-2 level than KET group. Conclusion: We found that siTUG1 decreased KET-induced hippocampal neurons apoptosis and ROS level, and increased hippocampal neurons viability. siTUG1 decreased neurons apoptosis via signaling pathways of Bax/Bcl-2 and Caspases, and increased neurons viability by signaling pathway of p38 MAPK. Our results indicate that KET-induced neurotoxicity might be reduced by inhibiting TUG1.
Entities:
Keywords:
Rat hippocampal neurons; TUG1; apoptosis; ketamine; viability