Ethyl pyruvate attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells: Role of GAS6/Axl signaling
Ying Chen,
Junmin Chen,
Lin Zhao,
Xin Zhang,
Xue Wu,
Xin Wang,
Zhe Zhang,
Yang Yang,
Chao Deng
Affiliations
Ying Chen
Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China
Junmin Chen
Department of Cardiology, Affiliated Hospital, Yan'an University, 43 North Street, Yan'an, 716000, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China
Lin Zhao
Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China
Xin Zhang
Department of Cardiology, Affiliated Hospital, Yan'an University, 43 North Street, Yan'an, 716000, China
Xue Wu
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China
Xin Wang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China
Zhe Zhang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China
Yang Yang
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China; Corresponding author. Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Chao Deng
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, 710069, Xi'an, China; Corresponding author. Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an 710061, China.
Background: Ischemic stroke, caused neurological dysfunction due to inadequate blood supply to brain, has a high morbidity and mortality. Ethyl pyruvate (EP), a simple aliphatic ester derived from pyruvic acid, has the advantages of safety and stability. Studies have confirmed that EP has anti-oxidative, anti-inflammation, anti-tumor, and other pharmacological effects, and it demonstrates significant therapeutic effects on multiple diseases. GAS6 and its high affinity Axl receptor play an important role in cell adhesion, anti-apoptosis, proliferation and migration by activating downstream signal transduction pathways. Previous studies have demonstrated the neuroprotective effects of the GAS6/Axl axis. Methods: A series of experimental methods were employed to confirm the effect of EP against cerebral hypoxia/reoxygenation (HR) injury. Results: In this study, the protective effect and mechanism of EP on HR injury in N2a cells was explored. The results found that treatment with EP could increase HR-injured neuronal viability, improve cell morphology, and reduce LDH release and ROS accumulation, thereby exhibiting a neuroprotective effect. Furthermore, EP treatment restored the down-regulated expression of GAS6, Axl, NQO1, PGC-1α, NRF1, and UCP2 caused by HR injury. Specifically, it was observed that the neuroprotective effect of EP was partially inhibited by GAS6 siRNA. Conclusion: In conclusion, these results suggest that EP treatment attenuates HR-induced oxidative stress injury in neuroblastoma cells via activating GAS6/Axl signaling.
