Identification of PRDX6 as a regulator of ferroptosis

生物 自噬
作者
Bin Lu,Xiaobing Chen,Yu-cai Hong,Hong Zhu,Qiaojun He,Bo Yang,Meidan Ying,Ji Cao
出处
期刊:Acta Pharmacologica Sinica 卷期号:40 (10): 1334-1342 被引量:31
标识
DOI:10.1038/s41401-019-0233-9
摘要

Ferroptosis is a newly characterized iron-dependent form of nonapoptotic regulated cell death triggered by lipid reactive oxygen species (LOOH). The dysregulation of ferroptosis is highly related to cancer, and the induction of ferroptosis is also proposed as a potential strategy for cancer therapy. Although several key regulators have been identified that are involved in ferroptosis, the molecular mechanism underlying this process remains largely unknown. Here, we report that Peroxiredoxin-6 (PRDX6) is a bona fide negative regulator of ferroptotic cell death. The knockdown of intracellular PRDX6 significantly enhances LOOH and ferroptotic cell death triggered by ferroptosis inducers (Erastin and RSL-3), which is correlated with the transcriptional activation of heme oxygenase-1. Moreover, overexpression of heme oxygenase-1 enhances both Erastin- and RSL-3-triggered LOOH, suggesting that heme oxygenase-1 mediates PRDX6 silencing-enhanced ferroptosis. More importantly, the application of a specific PRDX6 phospholipase A2 (iPLA2) inhibitor, MJ-33, synergistically enhances the ferroptosis induced by Erastin, suggesting that PRDX6 removes LOOH through its iPLA2 activity. Thus, our findings reveal an essential role of PRDX6 in protecting cells against ferroptosis and provide a potential target to improve the antitumor activity of ferroptosis-based chemotherapy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
YUan完成签到,获得积分10
刚刚
1秒前
阿巴阿巴发布了新的文献求助10
1秒前
3秒前
Joe发布了新的文献求助10
8秒前
贺呵呵完成签到 ,获得积分10
9秒前
LiuPP完成签到,获得积分0
10秒前
whl发布了新的文献求助10
10秒前
FATYE完成签到 ,获得积分10
11秒前
12秒前
13秒前
Joe完成签到,获得积分10
13秒前
16秒前
李爱国应助牙签撬地球采纳,获得10
16秒前
顾矜应助加到几点呢采纳,获得10
17秒前
19秒前
喜悦的尔风完成签到 ,获得积分10
21秒前
伊笙完成签到 ,获得积分10
23秒前
七月流火应助小卷粉采纳,获得50
23秒前
24秒前
Yosemite完成签到,获得积分10
26秒前
青城昊发布了新的文献求助10
26秒前
27秒前
30秒前
青城昊完成签到,获得积分10
31秒前
Yosemite发布了新的文献求助10
32秒前
星星点灯发布了新的文献求助10
32秒前
paulmichael完成签到,获得积分10
34秒前
砚明完成签到,获得积分10
36秒前
37秒前
未改完成签到,获得积分10
37秒前
suiyang完成签到,获得积分10
39秒前
40秒前
44秒前
脑洞疼应助汤圆软软软采纳,获得10
44秒前
suiyang发布了新的文献求助10
47秒前
小蘑菇应助芈钥采纳,获得10
54秒前
54秒前
昱旻完成签到,获得积分10
55秒前
56秒前
高分求助中
Heun’s Differential Equations 600
《Fundamentals of Power Supply Design》Robert A. Mammano 510
High Wire: How China Regulates Big Tech and Governs Its Economy 260
lingnan science journal vol. 16 250
The philosophy of sports medicine care: an historical review 250
A posteriori勾配制限手法「ポストリミタ」と界面捕獲法THINCを組み合わせた連続・不連続流れを高解像するMUSCLタイプの解法 210
遗传学与您的临床实践 200
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2251310
求助须知:如何正确求助?哪些是违规求助? 1900264
关于积分的说明 4742582
捐赠科研通 1689938
什么是DOI,文献DOI怎么找? 856841
版权声明 545529
科研通“疑难数据库(出版商)”最低求助积分说明 453765