Downregulation of FOXO4 promotes neuronal survival by mediating oxidative-stress–induced apoptosis after cerebral ischemia/reperfusion injury

作者：Chunying Deng, Peilan Zhang, Yun Zhang · 发表于：Tropical Journal of Pharmaceutical Research · 年份：2021 · DOI：10.4314/tjpr.v20i1.4 · 被引用次数：3 · 研究领域：FOXO transcription factor regulation、Mitochondrial Function and Pathology、MicroRNA in disease regulation

Purpose: To investigate the effect of FOXO4 on cerebral ischemia/reperfusion (CIR) injury and the underlying mechanism.Methods: An in vitro ischemia/reperfusion (IR) model was achieved using oxygen-glucose deprivation/reoxygenation (OGD/R). Expression of RNA and protein was determined using quantitative real time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Cell viability and apoptosis were determined using MTT assay and flow cytometry, respectively. Commercial kits were used to measure lactate dehydrogenase (LDH), reactive oxygen species (ROS), chloramphenicol acetyltransferase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD).Results: Following OGD/R, FOXO4 mRNA and protein expressions were upregulated in SH-SY5H human neuroblastoma cells. ODG/R reduced cell proliferation and increased the proportion of apoptotic cells, and these effects were inhibited by knockdown of FOXO4 (p < 0.05). Levels of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerases (PARPs) were increased after ODG/R and these increaseswere inhibited by FOXO4 knockdown. ROS content and levels of LDH and MDA were increased after ODG/R and decreased by knockdown of FOXO4 (p < 0.05). Levels of CAT and SOD were reduced after ODG/R, and this reduction was reversed by knockdown of FOXO4 (p < 0.05).Conclusion: The results demonstrate that knockdown of FOXO4 promotes cell proliferation and inhibits cellular apoptosis via reduction of oxidative stress after CIR inju...