Circ_0000115 Protects Against Cerebral Ischemia Injury by Suppressing Neuronal Apoptosis, Oxidative Stress and Inflammation by miR-1224-5p/Nos3 Axis In Vitro.

Autor: Cao Y; Department of Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, People's Republic of China., Xu Y; Department of Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, People's Republic of China., Zhang R; Department of Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, People's Republic of China., Qi J; Department of Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, 400038, People's Republic of China., Su Q; Department of Neurosurgery, The Fifth Clinical College of Chongqing Medical University, Chongqing, 400016, People's Republic of China., Chen Z; Department of Pediatrics, The First Affiliated Hospital of Army Medical University, No.30, Gaotanyan Street, Chongqing, 400038, People's Republic of China. chenzhiqiang_cc@163.com.
Jazyk: angličtina
Zdroj: Molecular biotechnology [Mol Biotechnol] 2024 May; Vol. 66 (5), pp. 1082-1094. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1007/s12033-023-01005-5
Abstrakt: Cerebral ischemia is a severe neurological disability related to neuronal apoptosis and cellular stress response. Circular RNAs (circRNAs) are emerging regulators of cerebral ischemia. Herein, this study proposed to probe the action of circ_0000115 in cerebral ischemia injury. The mouse neuroblastoma cells N2a and HT22 underwent oxygen-glucose deprivation (OGD) were used as a model of in vitro cerebral ischemia. Levels of genes and proteins were detected by qRT-PCR and western blotting. Cell proliferation and apoptosis were determined by EdU assay and flow cytometry. Western blotting was used to detect the protein level of pro-inflammatory factors. The oxidative stress injury was evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) generation. Dual-luciferase reporter and RIP assays were used to confirm the target relationship between miR-1224-5p and circ_0000115 or nitric oxide synthase 3 (NOS3). OGD exposure decreased circ_0000115 and NOS3 expression, and increased miR-1224-5p in N2a and HT22 cells in a time-dependent manner. Circ_0000115 silencing attenuated OGD-induced apoptosis, oxidative stress and inflammation in N2a and HT22 cells. Mechanistically, circ_0000115 directly sponged miR-1224-5p, which targeted NOS3. Furthermore, rescue experiments showed that miR-1224-5p overexpression abolished the neuroprotective effect of circ_0000115 in N2a and HT22 cells under OGD treatment. Besides that, silencing of miR-1224-5p protected N2a and HT22 cells against OGD-evoked injury, which was counteracted by NOS3 knockdown. Circ_0000115 protects N2a and HT22 cells against OGD-evoked neuronal apoptosis, inflammation, and oxidative stress via the miR-1224-5p/NOS3 axis, providing an exciting view of the pathogenesis of cerebral ischemia.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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