Free cholesterol-induced macrophage apoptosis is mediated by inositol-requiring enzyme 1 a

Free cholesterol-induced macrophage apoptosis is mediated by inositol-requiring enzyme 1 alpha-

regulated activation of Jun N-terminal kinase Fangming Li;Yi Guo;Shenggang Sun;Xin Jiang;Bingshan Tang;Qizhang Wang;Ling Wang 【期刊名称】《生物化学与生物物理学报：英文版》

【年(卷),期】2008(040)003

【摘要】Macrophage death in advanced atherosclerotic lesions leads to iesional necrosis, possible plaque rupture, and acute vascular occlusion.

A likely cause of macrophage death is the accumulation of free cholesterol (FC) leading to activation of endoplasmic reticulum (ER) stress-induced apoptosis.Inositol-requiring enzyme 1 alpha (IRE1α) is an integral membrane protein of the ER that is a key signaling step in cholesterol-induced apoptosis in macrophages, activated by stress in the ER. However, the role of IRE1α in the regulation of ER stress-induced macrophage death and the mechanism for this process are largely unclear.In this study,a cell culture model was used to explore the mechanisms involved in the ER stress pathway of FC-induced macrophage death.The results herein showed that FC loading of macrophages leads to an apoptotic response that is partially dependent on initiation by activation of IRE1α.Taken together,these results showed that the IRE1-apoptosis-signaling kinase 1-c-Jun NH2-terminal kinase cascade pathway was required in this process.Moreover,the data