title: Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage.
abstract: 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.
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Hanpeng
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ben
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Atherosclerosis Research Centre, Laboratory of Molecular Intervention for Cardiovascular Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, China;
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
keywords: ER stress; SR-A; apoptosis; autophagy; macrophage