Journal of neuro-oncology · 2026
BKCa channel deletion modulates the DNA damage response to electron ultra-high dose rate irradiation in glioblastoma cells.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Maliszewska-Olejniczak Kamila, Fryc Michał, Kustra Agata, Wiktorska Katarzyna, Lenartowicz-Gasik Aleksandra, Soroka Wojciech, Rzadkiewicz Jacek, Żochowska Monika, Kulawiak Bogusz, Bednarczyk Piotr
Аннотация
PURPOSE: Large-conductance Ca2 +-activated potassium (BKCa) channels have been implicated in glioblastoma progression and oxidative stress; however, their contribution to the cellular response to ionizing radiation remains poorly understood. Potassium channels represent attractive therapeutic targets because their activity can be modulated pharmacologically using selective inhibitors or genetically by gene silencing (siRNA) or gene knockout (CRISPR/Cas9). Here, we investigated whether genetic inhibition of BKCa modulates the DNA damage response of human glioblastoma cells following electron ultra-high dose rate (UHDR) irradiation.
METHODS: Human U87MG glioblastoma cells and BKCa-knockout cells (U87MG ΔαBKCa) were exposed to an electron UHDR-9 MeV beam with an average dose rate of 150 Gy/s. Clonogenic survival, reactive oxygen species levels, cell-cycle distribution, apoptosis, DNA-DSBs, DNA repair, and expression of selected genes encoding DDR pathways were analyzed.
RESULTS: BKCa deletion did not significantly alter clonogenic survival following UHDR irradiation. Cells lacking the BKCa channel exhibited elevated ROS levels, altered cell cycle distribution with G0/G1 accumulation, and enhanced apoptosis. UHDR induced lower γH2AX accumulation and reduced 53BP1 foci formation in U87MG ΔαBKCa cells, suggesting impaired DNA damage recognition and repair complex assembly. Gene expression analysis revealed a shift toward upregulation of DSBR pathways and downregulation of PARP-dependent SSBR mechanisms.
CONCLUSION: In conclusion, these findings identify BKCa as a regulator of the early molecular response of glioblastoma cells to electron UHDR irradiation and provide a basis for further studies investigating BKCa-dependent radiation responses as a target for therapeutic modulation.
METHODS: Human U87MG glioblastoma cells and BKCa-knockout cells (U87MG ΔαBKCa) were exposed to an electron UHDR-9 MeV beam with an average dose rate of 150 Gy/s. Clonogenic survival, reactive oxygen species levels, cell-cycle distribution, apoptosis, DNA-DSBs, DNA repair, and expression of selected genes encoding DDR pathways were analyzed.
RESULTS: BKCa deletion did not significantly alter clonogenic survival following UHDR irradiation. Cells lacking the BKCa channel exhibited elevated ROS levels, altered cell cycle distribution with G0/G1 accumulation, and enhanced apoptosis. UHDR induced lower γH2AX accumulation and reduced 53BP1 foci formation in U87MG ΔαBKCa cells, suggesting impaired DNA damage recognition and repair complex assembly. Gene expression analysis revealed a shift toward upregulation of DSBR pathways and downregulation of PARP-dependent SSBR mechanisms.
CONCLUSION: In conclusion, these findings identify BKCa as a regulator of the early molecular response of glioblastoma cells to electron UHDR irradiation and provide a basis for further studies investigating BKCa-dependent radiation responses as a target for therapeutic modulation.