Mechanism of irradiation-mediated mitophagy in vascular endothelial cell injury based on PINK1/Parkin signaling pathway
LU Xiaojiong
LIU Chenxi
WEN Wen
QUE Linfeng
CHEN Shuangjing
WANG Ying
JIN Zhitao
ZHANG Zheng
Abstract:Objective To establish a model of irradiation(Ir)injury of human umbilical vein endothelial cells(HUVECs),and discuss the mechanism of Ir-mediated mitophagy in vascular endothelial cell injury based on PINK1/Parkin signaling pathway.Methods Purchased HUVECs were divided into control group(0 Gy)and experimental groups(3 Gy,6 Gy,9 Gy,12 Gy).The cell viability was detected by using CCK-8 assay in each group,and cell apoptosis rate and levels of reactive oxygen species(ROS)were measured by using flow cytometry.The optimal Ir dose for model establishment was screened according to the above results.Based on the screening outcomes,9 Gy was selected as the modeling dose,and a control group and an Ir model group were set up.The ultrastructure of mitochondria was observed by using transmission electron microscopy in each group;cell migration rate cell was determined by using scratch assay;cell apoptosis index was detected by using TUNEL immunofluorescence staining.The expression levels of PINK1,Parkin,and LC3-II/LC3-I proteins were detected by using Western blotting assay.Results With the increase of Ir dose,cell viability showed a gradual decreasing trend,while cell apoptosis rate and ROS levels presented a gradual increasing trend.Compared with control group,the cell viability,apoptosis rate and ROS levels all had statistically significant differences in 3 Gy,6 Gy,9 Gy and 12 Gy groups(P<0.050).There were statistically significant differences in cell viability,apoptosis rate and ROS levels between 6 Gy group and 9 Gy group(P<0.050),while no statistically significant differences were found between 9 Gy group and 12 Gy group(P>0.050).When 9 Gy was selected as the modeling dose,compared with control group,the Ir model group exhibited obvious mitochondrial structural damage,reduced cell migration rate,increased cell apoptosis index,and significantly up-regulated expression levels of PINK1 and Parkin proteins as well as the LC3-II/LC3-I ratio(P<0.050).Conclusion Ir may induce HUVEC injury by activating the PINK1/Parkin signaling pathway and up-regulating mitophagy.
Keywords:irradiationvascular endothelial cellsmitophagyoxidative stress
Publication Date:2026-02-20
Online Publishing Date:2026-03-19(First online date of this platform, not the publication date of the document)
Pages:6( 217-221,227 )
