Cyclophilin A mediates the ox-LDL-induced activation and apoptosis of macrophages via autophagy

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• 作者：Zhiqiang Xue¹ ; Wei Yuan ; ¹ ; ^{yuanwei1@medmail.com.cn} ; Jing Li ; Hong Zhou ; Lihua Xu ; Jiayi Weng ; Xiaoyang Li ; Xinru Zhang ; Zhongqun Wang ; Jinchuan Yan ; ^{yanjinchuan@hotmail.com}
• 关键词：Atherosclerosis ; Macrophages ; CyclophilinA ; Oxidized low-density lipoprotein ; Apoptosis ; Autophagy
• 刊名：International Journal of Cardiology
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：230
• 期：Complete
• 页码：142-148
• 全文大小：1024 K
• 卷排序：230

文摘

Oxidized low-density lipoprotein (ox-LDL) is the most common inflammatory factor that mediates the activation and apoptosis of macrophages. Cyclophilin A (CyPA) is expressed following oxidative stress, hypoxia, and infection. However, the role of CyPA in the activation and apoptosis of macrophages is unclear. The aims of the study were to determine whether CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells and to analyze potential mechanisms.Methods and resultsThrough Western blot and ELISA test, the expression of CyPA induced by ox-LDL is time-dependent in RAW264.7 cells. Gene silencing of CyPA reduced the generation of lipid droplets in the cytoplasm and downregulated the expression of the surface markers of macrophage activation, namely, CD80, CD86, and major histocompatibility complex class 2 antigen. Cell apoptosis is significantly decreased and the level of anti-apoptosis protein bcl-2 is increased in CyPA silent cells compared with the control group. Finally, autophagy-related protein LC3-II/LC3-I ratio level significantly decreased in CyPA silent cells with less autophagosome formation while the blocked autophagy flux was recovered. The differences in the activation and apoptosis between CyPA silent cells and the control cells were inhibited by pre-treatment with class III PI 3-kinase inhibitor 3-MA.ConclusionsThese results indicate that CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells by regulating autophagy.