Huang Hanpeng, Li Xiaoyu, Zhuang Yan, Li Nan, Zhu Xudong, Hu Jin, Ben Jingjing, Yang Qing, Bai Hui, Chen Qi
Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China; ; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
J Biomed Res. 2014 May;28(3):213-21. doi: 10.7555/JBR.28.20130105. Epub 2013 Dec 12.
Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization. Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for cell survival under endoplasmic reticulum (ER) stress. We previously found that the engagement of class A scavenger receptor (SR-A) triggered JNK-dependent apoptosis in ER-stressed macrophages. However, pro-apoptotic mechanisms mediated by SR-A are not fully understood. Therefore, we sought to see if SR-A mediated apoptosis was associated with autophagy in macrophages. Here, we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates (LC3-II) formation as well as the number of autophagosomes under ER stress. The inhibition of LC3-II formation was paralleled by the activation of the mTOR pathway, and the inhibition of mTOR allowed LC3-II induction in macrophages treated with thapsigargin plus fucoidan. Furthermore, apoptosis induced by fucoidan was prevented under ER stress by the mTOR inhibitor. We propose that fucoidan, a SR-A agonist, may contribute to macrophage apoptosis during ER stress by inhibiting autophagy.
晚期动脉粥样硬化中巨噬细胞死亡会促进斑块坏死和不稳定。最近，自噬参与细胞成分的大量降解已被认为是内质网（ER）应激下细胞存活的重要机制。我们之前发现，A类清道夫受体（SR-A）的激活会触发内质网应激巨噬细胞中JNK依赖的凋亡。然而，SR-A介导的促凋亡机制尚未完全明确。因此，我们试图探究SR-A介导的凋亡是否与巨噬细胞中的自噬相关。在此，我们发现岩藻多糖在ER应激下抑制微管相关蛋白轻链3-磷脂共轭物（LC3-II）的形成以及自噬体的数量。LC3-II形成的抑制与mTOR通路的激活同时出现，并且mTOR的抑制使得在用毒胡萝卜素加岩藻多糖处理的巨噬细胞中诱导LC3-II。此外，在ER应激下，mTOR抑制剂可阻止岩藻多糖诱导的凋亡。我们认为，作为SR-A激动剂的岩藻多糖可能通过抑制自噬导致内质网应激期间巨噬细胞凋亡。
