Role of Orai3-Mediated Store-Operated Calcium Entry in Radiation-Induced Brain Microvascular Endothelial Cell Injury
-
Published:2023-04-06
Issue:7
Volume:24
Page:6818
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Wu Qibing1,
Fang Yang2,
Huang Xiaoyu1,
Zheng Fan2,
Ma Shaobo2,
Zhang Xinchen1,
Han Tingting1,
Gao Huiwen2,
Shen Bing2ORCID
Affiliation:
1. Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China
2. School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
Abstract
Radiation-induced brain injury is a serious complication with complex pathogenesis that may accompany radiotherapy of head and neck tumors. Although studies have shown that calcium (Ca2+) signaling may be involved in the occurrence and development of radiation-induced brain injury, the underlying molecular mechanisms are not well understood. In this study, we used real-time quantitative polymerase chain reaction and Western blotting assays to verify our previous finding using next-generation sequencing that the mRNA and protein expression levels of Orai3 in rat brain microvascular endothelial cells (rBMECs) increased after X-ray irradiation. We next explored the role of Orai3 and Orai3-mediated store-operated Ca2+ entry (SOCE) in radiation-induced brain injury. Primary cultured rBMECs derived from wild-type and Orai3 knockout (Orai3(−/−)) Sprague–Dawley rats were used for in vitro experiments. Orai3-mediated SOCE was significantly increased in rBMECs after X-ray irradiation. However, X-ray irradiation-induced SOCE increase was markedly reduced in Orai3 knockout rBMECs, and the percentage of BTP2 (a nonselective inhibitor of Orai channels)-inhibited SOCE was significantly decreased in Orai3 knockout rBMECs. Functional studies indicated that X-ray irradiation decreased rBMEC proliferation, migration, and tube formation (a model for assessing angiogenesis) but increased rBMEC apoptosis, all of which were ameliorated by BTP2. In addition, occurrences of all four functional deficits were suppressed in X-ray irradiation-exposed rBMECs derived from Orai3(−/−) rats. Cerebrovascular damage caused by whole-brain X-ray irradiation was much less in Orai3(−/−) rats than in wild-type rats. These findings provide evidence that Orai3-mediated SOCE plays an important role in radiation-induced rBMEC damage and brain injury and suggest that Orai3 may warrant development as a potential therapeutic target for reducing or preventing radiation-induced brain injury.
Funder
National Natural Science Foundation of China Regional Innovation and Development Joint Fund
Natural Science Foundation of Anhui Province
National Natural Science Foundation of China
Natural Science Foundation of Anhui Province Department of Education
National College Student Innovation and Entrepreneurship Training Program
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献