Neuroprotective Effects of Omentin-1 Against Cerebral Hypoxia/Reoxygenation Injury via Activating GAS6/Axl Signaling Pathway in Neuroblastoma Cells

Frontiers in Cell and Developmental Biology

Wenzhen Shi¹  Aizhen Zhao¹  Yang Yang¹  Meng Zhang¹  Luyang Du¹  Zhen Wu¹  Chenxi Lu¹  Changyu Wang¹  Xiaochen Niu¹  Baoping Ding¹  Ye Tian¹  Xue Wu¹  Xiyang Li¹  Shaofei Zhang¹  Ye Cheng¹  Shuai Liu¹ 

[1] Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi’an, China;Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine, Northwest University, Xi’an, China;

关键词: ischemic stroke;    omentin-1;    GAS6/TAM;    neuroprotection;    oxidative stress;   

DOI  :  10.3389/fcell.2021.784035

来源: DOAJ

【 摘 要 】

Ischemic stroke is characterized by insufficient blood supply to brain tissue and is associated with increased morbidity and mortality in adults worldwide. Growth arrest-specific protein 6 (GAS6) is a vitamin K-dependent protein and is widely expressed in the central nervous system. The biological functions of GAS6 are mediated by the interaction with TAM (Tyro3, Axl and Mertk) receptors, including cell survival and proliferation, immune regulation and apoptosis. Omentin-1, also known as intelectin-1 (ITLN-1), is a novel adipocytokine that is involved in a variety of biological events, such as insulin resistance, endothelial dysfunction, programmed cell death and metabolic disorders. Our previous study has found that omentin-1 act as a novel regulator of vascular and anti-apoptotic response in cerebral ischemia. However, the specific molecular mechanism of omentin-1’s protective effect on cerebral ischemia-reperfusion injury (IRI) is still unclear. First, the toxicity of recombinant human omentin-1 (rh-omentin) was assessed and a safe concentration was chosen for the next experiments. Then, rh-omentin exerted neuroprotection against hypoxia/reoxygenation (H/R) injury in N2a cells, indicated by increased cell viability, decreased LDH, ROS generation, and cell apoptotic rate. Furthermore, the similar protective effect was observed in omentin-1 overexpression cells constructed by lentivirus transfection. Rh-omentin could also inhibit H/R-induced apoptotic molecules, oxidative stress molecules, and GAS6/Axl signaling molecules which as evidence by increased omentin-1, GAS6, Axl, p-Axl, NQO1, HO-1, Nrf2, Bcl2 and decreased Bax expressions. However, GAS6 siRNA could reverse rh-omentin-induced neuroprotection and the levels of these molecules mentioned above. In conclusion, these findings suggest that omentin-1 treatment exerts neuroprotection against H/R injury partly via activating GAS6/Axl signaling at least. Therefore, these finding may favor omentin-1 a potential neuroprotective drug candidate to alleviate ischemia-reperfusion injury in clinic.

【 授权许可】

Unknown