PMID- 27363341
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20171126
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 477
IP  - 4
DP  - 2016 Sep 2
TI  - Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting 
      cIAPs-mediated inhibition of RIP1 and RIP3 activation.
PG  - 761-767
LID - S0006-291X(16)31059-2 [pii]
LID - 10.1016/j.bbrc.2016.06.132 [doi]
AB  - Apoptotic and necrotic macrophages have long been known for their existence in 
      atherosclerotic lesions. However, the mechanisms underlying the choice of their 
      death pattern have not been fully elucidated. Here, we report the effects of 
      PS-341, a potent and specific proteasome inhibitor, on the cell death of primary 
      bone marrow-derived macrophages (BMDMs) in vitro. The results showed that PS-341 
      could not induce macrophage apoptosis or promote TNF-induced macrophage 
      apoptosis, on the other hand, PS-341 could significantly inhibit macrophage 
      necroptosis induced by TNF and pan-caspase inhibitor z-VAD treatment. Remarkably, 
      high-dose of PS-341 showed similar inhibitory effects on macrophage necroptosis 
      comparable to that of kinase inhibition of RIP1 through specific inhibitor Nec-1 
      or inhibition of RIP3 via specific genetical ablation. Furthermore, the 
      degradation of cellular inhibitor of apoptosis proteins (cIAPs) was suppressed by 
      PS-341, which could antagonize the activation of RIP1 kinase via 
      post-translational mechanism. Further evidences demonstrated reduced levels of 
      both RIP1 and RIP 3 upon PS-341 treatment, concomitantly, a more strong 
      association of RIP1 with cIAPs and less with RIP3 was found following PS-341 
      treatment, these findings suggested that PS-341 may disrupt the formation of 
      RIP1-RIP3 complex (necrosome) through stabilizing cIAPs. Collectively, our 
      results indicated that the proteasome-mediated degradation of cIAPs could be 
      inhibited by PS-341 and followed by limited RIP1 and RIP3 kinase activities, 
      which were indispensable for necroptosis, thus eliciting a significant 
      necroptosis rescue in BMDMs in vitro. Overall, our study has identified a new 
      role of PS-341 in the cell death of BMDMs and provided a novel insight into the 
      atherosclerotic inflammation caused by proteasome-mediated macrophage 
      necroptosis.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Zhang, Yuchen
AU  - Zhang Y
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Cheng, Junjun
AU  - Cheng J
AD  - Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & 
      Peking Union Medical College, Beijing, 100050, China.
FAU - Zhang, Junmeng
AU  - Zhang J
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Wu, Xiaofan
AU  - Wu X
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Chen, Fang
AU  - Chen F
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Ren, Xuejun
AU  - Ren X
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Wang, Yunlong
AU  - Wang Y
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Li, Quan
AU  - Li Q
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China.
FAU - Li, Yu
AU  - Li Y
AD  - Department of Cardiology, Beijing An Zhen Hospital of the Capital University of 
      Medical Sciences, Beijing, 100029, China. Electronic address: lybjazh@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160627
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Proteasome Inhibitors)
RN  - 69G8BD63PP (Bortezomib)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Bortezomib/*administration & dosage
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Macrophages/drug effects/*metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Necrosis
MH  - Proteasome Endopeptidase Complex/drug effects/metabolism
MH  - Proteasome Inhibitors/*administration & dosage
MH  - Receptor-Interacting Protein Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Macrophage
OT  - Necroptosis
OT  - PS-341
EDAT- 2016/07/02 06:00
MHDA- 2017/05/16 06:00
CRDT- 2016/07/02 06:00
PHST- 2016/06/17 00:00 [received]
PHST- 2016/06/26 00:00 [accepted]
PHST- 2016/07/02 06:00 [entrez]
PHST- 2016/07/02 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
AID - S0006-291X(16)31059-2 [pii]
AID - 10.1016/j.bbrc.2016.06.132 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Sep 2;477(4):761-767. doi: 
      10.1016/j.bbrc.2016.06.132. Epub 2016 Jun 27.