GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression
GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression
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DOI：
10.1016/j.bbrc.2020.03.079
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发表时间：
2020-05-28
影响因子：
3.1
通讯作者：
Sun, Xiuju
中科院分区：
文献类型：
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作者：
Chen, Liang;Qiao, Linlin;Sun, Xiuju
铁凋亡是一种铁依赖性的调节性细胞死亡。GDF 15影响癌细胞的各种性质，但GDF 15在铁凋亡中的作用尚未报道。在本研究中，我们发现GDF 15敲低导致SLC 7A 11表达减少，SLC 7A 11是X-c（-）系统的关键组分，也是铁凋亡的调节因子，表明GDF 15可能在铁凋亡中起重要作用。CCK-8法显示GDF 15基因敲低可促进erastin诱导的MGC 803细胞铁凋亡。qRT-PCR和蛋白质印迹结果表明，GDF 15抑制减弱了erastin诱导的SLC 7A 11表达增加。进一步的研究表明，GDF 15敲低促进了细胞外谷氨酸和细胞内GSH水平的降低，以及在erastin存在下的脂质ROS水平的增加。总体而言，该研究表明，GDF 15敲除通过减弱SLC 7A 11的表达和系统X-c（-）的功能来促进erastin诱导的MGC 803细胞铁细胞凋亡。(C)2020爱思唯尔公司All rights reserved.
Ferroptosis is an iron-dependent form of regulated cell death. GDF15 affects various properties of cancer cells, but the role of GDF15 in ferroptosis has not been reported. In the present study, we found that GDF15 knockdown led to decreased expression of SLC7A11, which is a key component of system X-c(-) and a regulator of ferroptosis, indicating that GDF15 might play important roles in ferroptosis. CCK8 assay showed that GDF15 knockdown promoted erastin-induced ferroptosis in MGC803 cells. qRT-PCR and western blotting results demonstrated that GDF15 inhibition attenuated the increased SLC7A11 expression induced by erastin. Further study revealed that GDF15 knockdown promoted the decreased level of extracellular glutamate and intracellular GSH as well as the increased level of lipid ROS in the presence of erastin in MGC803 cells. Overall, the study shows that GDF15 knockdown promotes erastin-induced ferroptosis in MGC803 cells by attenuating the expression of SLC7A11 and the function of system X-c(-). (C) 2020 Elsevier Inc. All rights reserved.