Brain research bulletin · 2025
Verbascoside inhibits OGD/R-induced SK-N-SH cell injury by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway.
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Wen Liwei, Zhang Cheng, Zhou Xia, Feng Jiaxing, Li Qiang, Yang Fubing
Аннотация
BACKGROUND: The potential therapeutic value of verbascoside (VB) has been reported in a variety of diseases, including cerebral hemorrhage. In this study, we aimed to explore the underlying mechanism of VB in cerebral ischemic stroke.
METHODS: The in vitro ischemic stroke model was established by Oxygen-glucose deprivation/reoxygenation (OGD/R) model. CCK-8 assay and EdU assay were performed for cell proliferation. Flow cytometry analysis was adopted to analyze cell apoptosis. ELISA kits were used to estimate the concentrations of inflammatory factors. Ferroptosis-related markers were examined with indicated commercial kits. The relations of METTL14, CHAC1 and IGF2BP2 were analyzed by MeRIP assay, RIP assay and Actinomycin D assay. Gene expression was determined by qRT-PCR and western blot.
RESULTS: VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells. VB decreased METTL14 expression in OGD/R-treated SK-N-SH cells and METTL14 knockdown alleviated OGD/R-induced injury of SK-N-SH cells. METTL14 and IGF2BP2 mediates m6A modification of CHAC1. CHAC1 overexpression abrogated the effects of METTL14 knockdown on OGD/R-induced SK-N-SH cell injury. Moreover, the effects of VB on OGD/R-treated SK-N-SH cell proliferation, apoptosis, inflammation and ferroptosis were abated by elevating METTL14 or CHAC1. Besides, VB reduced the levels of NRF2, SLC7A11 and GPX4 in OGD/R-treated SK-N-SH cells, while METTL14 or CHAC1 overexpression reversed the effects.
CONCLUSION: VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway.
METHODS: The in vitro ischemic stroke model was established by Oxygen-glucose deprivation/reoxygenation (OGD/R) model. CCK-8 assay and EdU assay were performed for cell proliferation. Flow cytometry analysis was adopted to analyze cell apoptosis. ELISA kits were used to estimate the concentrations of inflammatory factors. Ferroptosis-related markers were examined with indicated commercial kits. The relations of METTL14, CHAC1 and IGF2BP2 were analyzed by MeRIP assay, RIP assay and Actinomycin D assay. Gene expression was determined by qRT-PCR and western blot.
RESULTS: VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells. VB decreased METTL14 expression in OGD/R-treated SK-N-SH cells and METTL14 knockdown alleviated OGD/R-induced injury of SK-N-SH cells. METTL14 and IGF2BP2 mediates m6A modification of CHAC1. CHAC1 overexpression abrogated the effects of METTL14 knockdown on OGD/R-induced SK-N-SH cell injury. Moreover, the effects of VB on OGD/R-treated SK-N-SH cell proliferation, apoptosis, inflammation and ferroptosis were abated by elevating METTL14 or CHAC1. Besides, VB reduced the levels of NRF2, SLC7A11 and GPX4 in OGD/R-treated SK-N-SH cells, while METTL14 or CHAC1 overexpression reversed the effects.
CONCLUSION: VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway.