中国病理生理杂志2024，Vol.40Issue(6)：1033-1042,10.DOI:10.3969/j.issn.1000-4718.2024.06.009
罗汉果皂苷V对RSL3诱导的SH-SY5Y细胞铁死亡的抑制作用及其机制
Inhibitory effect of mogroside V on RSL3-induced ferroptosis of SH-SY5Y cells and its mechanism
摘要
Abstract
AIM:To investigate the inhibitory effect of mogroside V(MV)on ferroptosis of human neuroblas-toma SH-SY5Y cells induced by RAS-selective lethal 3(RSL3),and to explore its possible mechanism.METHODS:To establish a model of ferroptosis,the SH-SY5Y cell was induced by RSL3.The cell viability and cellular morphology were determined by MTT assay and inverted microscopy,respectively.The intracellular ferrous ion content was measured by ferrous ion fluorescence probe FerrOrange.Mitochondrial membrane potential(MMP)was detected by mitochondrial red fluorescent probe MitoTracker Red CMXRos.The intracellular and mitochondrial reactive oxygen species(ROS)were de-tected by superoxide anion fluorescent probe dihydroethidium and mitochondrial superoxide red fluorescent probe MitoSOX Red,respectively.The cellular glutathione(GSH)and malondialdehyde(MDA)levels were tested by microplate assay.The protein levels of acyl-coenzyme A synthetase long-chain family member 4(ACSL4),cyclooxygenase-2(COX-2),glu-tathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.Molecu-lar docking techniques were employed to predict the targeting relations between MV and ACSL4/COX-2/GPX4/SLC7A11.RESULTS:Compared with control group,the SH-SY5Y cell viability,the MMP and the GSH level in RSL3 group were significantly reduced(P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels and the MDA level were significantly increased(P<0.05 or P<0.01).The protein levels of ACSL4 and COX-2 in RSL3 group were significantly increased,while the protein levels of GPX4 and SLC7A11 were significantly decreased(P<0.01),indicating the establishment of cell ferroptosis model.Compared with RSL3 group,the viability of SH-SY5Y cells,the MMP,the GSH level,and the GPX4 and SLC7A11 protein levels in RSL3+MV groups were significantly in-creased(P<0.05 or P<0.01),while the intracellular ferrous ion level,the intracellular and mitochondrial ROS levels,the MDA level,and the ACSL4 and COX-2 protein levels were significantly decreased(P<0.05 or P<0.01).The binding sites between MV and ferroptosis core proteins(ACSL4,COX-2,GPX4 and SLC7A11)were found by molecular docking.CONCLUSION:Treatment with MV alleviates RSL3-induced ferroptosis of SH-SY5Y cells,and the underlying mecha-nism may be associated with the activation of SLC7A11/GPX4 and the inhibition of ACSL4/COX-2.关键词
罗汉果皂苷V/神经母细胞瘤/RSL3化合物/铁死亡/SLC7A11/GPX4信号通路Key words
mogroside V/neuroblastoma/ferroptosis/RSL3 compound/SLC7A11/GPX4 signaling pathway分类
医药卫生引用本文复制引用
刘艳,夏荣松,冉冬芝,彭哲,王红..罗汉果皂苷V对RSL3诱导的SH-SY5Y细胞铁死亡的抑制作用及其机制[J].中国病理生理杂志,2024,40(6):1033-1042,10.基金项目
重庆市留学回国创业创新支持计划(No.X10419) （No.X10419）
