Article ; Online: FGIN-1-27 Mitigates Radiation-induced Mitochondrial Hyperfunction and Cellular Hyperactivation in Cultured Astrocytes.
2023 Volume 535, Page(s) 23–35
Abstract: Radiation-induced brain injury (RBI) poses a significant challenge in the context of radiotherapy for intracranial tumors, necessitating a comprehensive understanding of the cellular and molecular mechanisms involved. While prior investigations have ... ...
| Abstract | Radiation-induced brain injury (RBI) poses a significant challenge in the context of radiotherapy for intracranial tumors, necessitating a comprehensive understanding of the cellular and molecular mechanisms involved. While prior investigations have underscored the role of astrocyte activation and excessive vascular endothelial growth factor production in microvascular damage associated with RBI, there remains a scarcity of studies examining the impact of radiation on astrocytes, particularly regarding organelles such as mitochondria. Thus, our study aimed to elucidate alterations in astrocyte and mitochondrial functionality following radiation exposure, with a specific focus on evaluating the potential ameliorative effects of translocator protein 18 kDa(TSPO) ligands. In this study, cultured astrocytes were subjected to X-ray irradiation, and their cellular states and mitochondrial functions were examined and compared to control cells. Our findings revealed that radiation-induced astrocytic hyperactivation, transforming them into the neurotoxic A1-type, concomitant with reduced cell proliferation. Additionally, radiation triggered mitochondrial hyperfunction, heightened the mitochondrial membrane potential, and increased oxidative metabolite production. However, following treatment with FGIN-1-27, a TSPO ligand, we observed a restoration of mitochondrial function and a reduction in oxidative metabolite production. Moreover, this intervention mitigated astrocyte hyperactivity, decreased the number of A1-type astrocytes, and restored cell proliferative capacity. In conclusion, our study has unveiled additional manifestations of radiation-induced astrocyte dysfunction and validated that TSPO ligands may serve as a promising therapeutic strategy to mitigate this dysfunction. It has potential clinical implications for the treatment of RBI. |
|---|---|
| MeSH term(s) | Astrocytes/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Mitochondria/metabolism ; Indoleacetic Acids/metabolism ; Indoleacetic Acids/pharmacology ; Cells, Cultured ; Carrier Proteins/metabolism |
| Chemical Substances | N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide (142720-24-9) ; Vascular Endothelial Growth Factor A ; Indoleacetic Acids ; Carrier Proteins |
| Language | English |
| Publishing date | 2023-10-31 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 196739-3 |
| ISSN | 1873-7544 ; 0306-4522 |
| ISSN (online) | 1873-7544 |
| ISSN | 0306-4522 |
| DOI | 10.1016/j.neuroscience.2023.10.017 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1215: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.