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

doi:10.1016/j.heliyon.2023.e22787

Ethyl pyruvate attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells: Role of GAS6/Axl signaling

Heliyon. 2023 Nov 23;9(12):e22787. doi: 10.1016/j.heliyon.2023.e22787. eCollection 2023 Dec.

Authors

Ying Chen^{1

2}, Junmin Chen^{3

4}, Lin Zhao⁵, Xin Zhang³, Xue Wu⁴, Xin Wang⁴, Zhe Zhang⁴, Yang Yang⁴, Chao Deng⁴

Affiliations

¹ Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
² Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
³ Department of Cardiology, Affiliated Hospital, Yan'an University, 43 North Street, Yan'an, 716000, China.
⁴ 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.
⁵ Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.

Abstract

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.

Keywords: Axl; Ethyl pyruvate; GAS6; Hypoxia/Reoxygenation injury; Neuroblastoma cells.