Role of YAP/OPA1 signaling pathway in propofol-induced reduction of oxygen-glucose deprivation and restoration injury in hippocampal neurons
10.3760/cma.j.cn131073.20230220.00818
- VernacularTitle:YAP/OPA1信号通路在丙泊酚减轻小鼠海马神经元氧糖剥夺-复氧复糖损伤中的作用
- Author:
Zehua WANG
1
;
Xiaoyan MA
;
Wenli YU
Author Information
1. 长治医学院麻醉学系，长治 046000
- Keywords:
Propofol;
Neurons;
Reperfusion injury;
Yes-associated protein;
Optic atrophy-1
- From:
Chinese Journal of Anesthesiology
2023;43(8):986-990
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the role of Yes-associated protein (YAP)/Optic atrophy-1 (OPA1) signaling pathway in propofol-induced reduction of oxygen-glucose deprivation and restoration(OGD/R) injury in hippocampal neurons.Methods:HT22 mouse hippocampal neurons at the logarithmic growth phase were divided into 4 groups ( n=54 each) using a random number table method: control group (group C), group OGD/R, propofol group (group P) and propofol + YAP silencing group (group P + siRNA-YAP). The cells were subjected to O 2-glucose deprivation for 6 h followed by restoration of O 2-glucose supply for 24 h. In group P, propofol 50 μmol/L was added immediately after restoration of O 2-glucose supply. In P+ siRNA-YAP group, siRNA-YAP was transfected at 48 h before model preparation. The viability of neurons was measured by CCK-8 assay, ROS content and apoptosis rate were measured by flow cytometry, the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) were determined by spectrophotometry, the content of mitochondrial ATP was determined by fluorescein fluorescence method, the nuclear translocation of YAP was observed by immunofluorescence, and the expression of YAP, phosphorylated YAP (p-YAP) and OPA1 was detected by Western blot. Results:Compared with group C, the viability of hippocampal neurons was significantly decreased, the contents of ROS and MDA and apoptosis rate were increased, the SOD activity, MMP and mitochondrial ATP content were decreased, the expression of p-YAP protein was up-regulated, OPA1 expression was down-regulated ( P<0.05), and the fluorescence intensity of YAP in nucleus was weakened in group OGD/R. Compared with OGD/R group, the viability of neurons was significantly increased, the contents of ROS and MDA and apoptosis rate were decreased, the activity of SOD, MMP and content of mitochondrial ATP were increased, the expression of p-YAP protein was down-regulated, the expression of OPA1 protein was up-regulated( P<0.05), and the fluorescence intensity of YAP in nucleus was enhanced in P group. Compared with group P, the viability of neurons was significantly decreased, the contents of ROS and MDA and apoptosis rate were increased, the SOD activity, MMP and mitochondrial ATP content were decreased, the expression of p-YAP, YAP and OPA1 was down-regulated ( P<0.05), and the fluorescence intensity of YAP in nucleus was weakened in group P+ siRNA-YAP. Conclusions:The mechanism by which propofol reduces OGD/R injury in hippocampal neurons may be related to activation of YAP/OPA1 signaling pathway.
