Guangming Su1, Wei Yang2, Shengjiao Wang3, Chunhui Geng4, Xiuru Guan5. 1. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, NanGang, Harbin, Heilongjiang, 150001, PR China. Electronic address: 569676915@qq.com. 2. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, NanGang, Harbin, Heilongjiang, 150001, PR China. Electronic address: yangwei6295@163.com. 3. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, NanGang, Harbin, Heilongjiang, 150001, PR China. Electronic address: 913111793@qq.com. 4. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, NanGang, Harbin, Heilongjiang, 150001, PR China. Electronic address: 737664511@163.com. 5. Department of Laboratory Diagnostics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, NanGang, Harbin, Heilongjiang, 150001, PR China. Electronic address: gxr0451@sina.com.
Abstract
OBJECTIVE: Ferroptosis is a new form of programmed cell death characterized by an iron-dependent increase in lipid ROS. It has recently been reported that elevated iron levels in macrophages in plaques are associated with atherosclerosis(AS). However, it is not clear whether iron induces ferroptosis and the mechanism of ferroptosis induced by iron in macrophages in plaque. METHODS: THP-1 macrophages were treated with ox-LDL and ferric ammonium citrate(FAC). Activate SIRT1 using SRT1720. Use of RAPA and CQ to promote and suppress autophagy. The expression of SIRT1, GPX4 was detected by Western Blot, and the cell activity and lipid ROS level were also performed. IL-1β and IL-18 levels were measured using qRT-PCR and ELISA. RESULTS: In this study, we determined that FAC can induce a decrease in foam cell activity rather than macrophage activity, increase lipid ROS levels, decrease GPX4 expression and inhibit SIRT1 expression, and increase IL-1β and IL-18 levels. SRT1720 activated SIRT1 and reversed the above changes induced by FAC. CQ partially prevents the above changes caused by activating SIRT1. CONCLUSION: Activation of SIRT1 can inhibit the ferroptosis and IL-1β and IL-18 levels of foam cells in excess iron by autophagy, providing a novel therapeutic target for AS.
OBJECTIVE: Ferroptosis is a new form of programmed cell death characterized by an iron-dependent increase in lipid ROS. It has recently been reported that elevated iron levels in macrophages in plaques are associated with atherosclerosis(AS). However, it is not clear whether iron induces ferroptosis and the mechanism of ferroptosis induced by iron in macrophages in plaque. METHODS:THP-1 macrophages were treated with ox-LDL and ferric ammonium citrate(FAC). Activate SIRT1 using SRT1720. Use of RAPA and CQ to promote and suppress autophagy. The expression of SIRT1, GPX4 was detected by Western Blot, and the cell activity and lipid ROS level were also performed. IL-1β and IL-18 levels were measured using qRT-PCR and ELISA. RESULTS: In this study, we determined that FAC can induce a decrease in foam cell activity rather than macrophage activity, increase lipid ROS levels, decrease GPX4 expression and inhibit SIRT1 expression, and increase IL-1β and IL-18 levels. SRT1720 activated SIRT1 and reversed the above changes induced by FAC. CQ partially prevents the above changes caused by activating SIRT1. CONCLUSION: Activation of SIRT1 can inhibit the ferroptosis and IL-1β and IL-18 levels of foam cells in excess iron by autophagy, providing a novel therapeutic target for AS.
Authors: Dijana Stojanovic; Miodrag Stojanovic; Jelena Milenkovic; Aleksandra Velickov; Aleksandra Ignjatovic; Maja Milojkovic Journal: Oxid Med Cell Longev Date: 2022-09-12 Impact factor: 7.310