Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage.
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage.
复制标题
A 类清道夫受体激活抑制巨噬细胞中内质网应激诱导的自噬。
DOI：
10.7555/jbr.28.20130105
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发表时间：
2014-05
影响因子：
2.3
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Huang H;Li X;Zhuang Y;Li N;Zhu X;Hu J;Ben J;Yang Q;Bai H;Chen Q
晚期动脉粥样硬化中的巨噬细胞死亡促进斑块坏死和不稳定。自噬参与细胞组分的大量降解是内质网应激下细胞存活的重要机制。我们以前发现，A类清道夫受体（SR-A）的参与触发JNK依赖性细胞凋亡在ER应激的巨噬细胞。然而，SR-A介导的促凋亡机制尚未完全了解。因此，我们试图了解SR-A介导的细胞凋亡是否与巨噬细胞中的自噬相关。在这里，我们发现岩藻依聚糖抑制微管相关蛋白轻链3-磷脂缀合物（LC 3-II）的形成以及ER应激下自噬体的数量。LC 3-II形成的抑制被mTOR途径的激活所抵消，并且mTOR的抑制允许用毒胡萝卜素加岩藻依聚糖处理的巨噬细胞中的LC 3-II诱导。此外，岩藻依聚糖诱导的细胞凋亡在ER应激下被mTOR抑制剂阻止。我们认为，岩藻依聚糖，一种SR-A激动剂，可能有助于巨噬细胞凋亡过程中ER应激抑制自噬。
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.