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铁死亡与凋亡之间的分子串扰：内质网应激诱导的不依赖p53的PUMA表达的新作用

Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression.

作者信息

Hong Se Hoon, Lee Dae-Hee, Lee Young-Sun, Jo Min Jee, Jeong Yoon A, Kwon William T, Choudry Haroon A, Bartlett David L, Lee Yong J

机构信息

Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 02841, Republic of Korea.

出版信息

Oncotarget. 2017 Dec 8;8(70):115164-115178. doi: 10.18632/oncotarget.23046. eCollection 2017 Dec 29.

DOI:10.18632/oncotarget.23046
PMID:29383150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5777762/
Abstract

Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and BxPC-3 and human colorectal cancer HCT116 cells were treated with ferroptotic agents such as erastin and artesunate (ART) in combination with the apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed synergistic interaction of erastin or ART with TRAIL as determined by cell death assay, caspase activation, poly [ADP-ribose] polymerase 1 (PARP-1) cleavage, flow cytometry analysis, and lipid peroxidation assay. Moreover, erastin and ART induced endoplasmic reticulum (ER) stress and promoted p53 upregulated modulator of apoptosis (PUMA) expression via C/EBP-homologous protein (CHOP). Synergy of erastin/ART and TRAIL was abolished in PUMA-deficient HCT116 cells and CHOP-deficient mouse embryonic fibroblasts, but not in p53-deficient HCT116 cells. The results suggest the involvement of the p53-independent CHOP/PUMA axis in response to ferroptosis inducers, which may play a key role in ferroptotic agent-mediated sensitization to TRAIL-induced apoptosis.

摘要

铁死亡是一种依赖铁的程序性细胞死亡，其特征是脂质过氧化物的积累。在本研究中，我们调查了铁死亡与其他形式的细胞死亡（如凋亡）之间相互作用的本质。使用铁死亡诱导剂（如艾拉司群和青蒿琥酯（ART））联合凋亡诱导剂肿瘤坏死因子相关凋亡诱导配体（TRAIL）处理人胰腺癌PANC-1和BxPC-3细胞以及人结直肠癌HCT116细胞。通过细胞死亡检测、半胱天冬酶激活、聚[ADP-核糖]聚合酶1（PARP-1）裂解、流式细胞术分析和脂质过氧化检测，我们观察到艾拉司群或ART与TRAIL之间存在协同相互作用。此外，艾拉司群和ART诱导内质网（ER）应激，并通过C/EBP同源蛋白（CHOP）促进凋亡调节蛋白p53上调（PUMA）的表达。在PUMA缺陷的HCT116细胞和CHOP缺陷的小鼠胚胎成纤维细胞中，艾拉司群/ART与TRAIL的协同作用被消除，但在p53缺陷的HCT116细胞中未被消除。结果表明，p53非依赖性的CHOP/PUMA轴参与了对铁死亡诱导剂的反应，这可能在铁死亡诱导剂介导的对TRAIL诱导凋亡的敏感性中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/56f0170c61c1/oncotarget-08-115164-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/e57b4078def9/oncotarget-08-115164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/3ed11830d61c/oncotarget-08-115164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/9afda1434ac8/oncotarget-08-115164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/1df4be54cc29/oncotarget-08-115164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/a631f7b38979/oncotarget-08-115164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/e610561f94d1/oncotarget-08-115164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/299a7f49a828/oncotarget-08-115164-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/56f0170c61c1/oncotarget-08-115164-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/e57b4078def9/oncotarget-08-115164-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/3ed11830d61c/oncotarget-08-115164-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/9afda1434ac8/oncotarget-08-115164-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/1df4be54cc29/oncotarget-08-115164-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/a631f7b38979/oncotarget-08-115164-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/e610561f94d1/oncotarget-08-115164-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/299a7f49a828/oncotarget-08-115164-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b3/5777762/56f0170c61c1/oncotarget-08-115164-g008.jpg

相似文献

[1]
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[2]
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[3]
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本文引用的文献

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