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

被引:17
|
作者
Niu, Xiaochen [1 ,2 ]
Cheng, Ye [1 ,2 ]
Zhang, Meng [1 ,2 ]
Du, Luyang [1 ,2 ]
Wu, Xue [1 ,2 ]
Lu, Chenxi [1 ,2 ]
Li, Xiyang [1 ,2 ]
Liu, Shuai [1 ,2 ]
Zhao, Aizhen [1 ,2 ]
Zhang, Shaofei [1 ,2 ]
Wu, Zhen [1 ,2 ]
Ding, Baoping [1 ,2 ]
Shi, Wenzhen [1 ,2 ]
Wang, Changyu [1 ,2 ]
Yang, Yang [1 ,2 ]
Tian, Ye [1 ,2 ]
机构
[1] Northwest Univ, Xian Hosp 3, Sch Life Sci & Med, Xian Key Lab Cardiovasc & Cerebrovasc Dis,Affilia, Xian, Peoples R China
[2] Northwest Univ, Fac Life Sci, Key Lab Resource Biol & Biotechnol Western China, Minist Educ, Xian, Peoples R China
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2022年 / 9卷
基金
中国国家自然科学基金;
关键词
ischemic stroke; omentin-1; GAS6; TAM; neuroprotection; oxidative stress; ACUTE ISCHEMIC-STROKE; ADIPOSE-TISSUE; EXPRESSION; OXYGEN; AXL;
D O I
10.3389/fcell.2021.784035
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
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.
引用
收藏
页数:15
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