The International journal of neuroscience · 2026
miR-4508 targets PLCB2 in propofol-induced neurotoxicity in sH-SY5Y cells: role and mechanism.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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.
Zhan Zhenbin, Chen Hai, Chen Jinguang
Аннотация
OBJECTIVE: Propofol is a widely administered anesthetic agent given intravenously. This study investigated the function of miR-4508 within propofol-elicited neurotoxicity in SH-SY5Y cells, identified its downstream target genes, and elucidated the underlying molecular regulatory pathway.
METHODS: Propofol neurotoxicity was modeled in SH-SY5Y cells with varying concentrations and durations. Cell viability, miR-4508, oxidative stress, and inflammatory cytokines were measured. Target prediction and dual-luciferase validation, along with miRNA inhibitor and rescue experiments, were used to elucidate the regulatory mechanism. Cognitive function and hippocampal miR-4508 expression were also preliminarily assessed in propofol-exposed mice using the Morris water maze and RT-qPCR, respectively.
RESULTS: Propofol reduced SH-SY5Y cell viability and upregulated miR-4508 in a manner dependent on both concentration and time, peaking at 50 μM for 24 h. Five candidate targets were identified bioinformatically. PLCB2 was most downregulated by miR-4508 overexpression. A dual-luciferase assay verified that miR-4508 directly binds to the PLCB2 3'-UTR. A miR-4508 inhibitor attenuated propofol-induced oxidative stress and inflammation, effects reversed by PLCB2 knockdown. Preliminary in vivo observations suggested impaired learning/memory and increased hippocampal miR-4508 in propofol-treated mice, with miR-4508 inhibition showing a tendency toward reversal of these deficits, though further validation is required.
CONCLUSIONS: This study demonstrates that propofol upregulates miR-4508 to suppress PLCB2, driving oxidative stress and neuroinflammation. Forward and reverse rescue experiments confirm the miR-4508/PLCB2 axis as a potential therapeutic target for propofol-induced neurotoxicity.
METHODS: Propofol neurotoxicity was modeled in SH-SY5Y cells with varying concentrations and durations. Cell viability, miR-4508, oxidative stress, and inflammatory cytokines were measured. Target prediction and dual-luciferase validation, along with miRNA inhibitor and rescue experiments, were used to elucidate the regulatory mechanism. Cognitive function and hippocampal miR-4508 expression were also preliminarily assessed in propofol-exposed mice using the Morris water maze and RT-qPCR, respectively.
RESULTS: Propofol reduced SH-SY5Y cell viability and upregulated miR-4508 in a manner dependent on both concentration and time, peaking at 50 μM for 24 h. Five candidate targets were identified bioinformatically. PLCB2 was most downregulated by miR-4508 overexpression. A dual-luciferase assay verified that miR-4508 directly binds to the PLCB2 3'-UTR. A miR-4508 inhibitor attenuated propofol-induced oxidative stress and inflammation, effects reversed by PLCB2 knockdown. Preliminary in vivo observations suggested impaired learning/memory and increased hippocampal miR-4508 in propofol-treated mice, with miR-4508 inhibition showing a tendency toward reversal of these deficits, though further validation is required.
CONCLUSIONS: This study demonstrates that propofol upregulates miR-4508 to suppress PLCB2, driving oxidative stress and neuroinflammation. Forward and reverse rescue experiments confirm the miR-4508/PLCB2 axis as a potential therapeutic target for propofol-induced neurotoxicity.