Defining the functions and translational potential of ferroptosis

定义铁死亡的功能和转化潜力

• 批准号: 10478855
• 负责人: Brent R Stockwell
• 金额: $ 92.65万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-02 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478855
• 关键词: Automobile Driving; Cell Death; Goals; Lipid Peroxidation; Lipids; Malignant Neoplasms; Nutrient; Oxidative Stress; Pathway interactions; Process; Research; Signal Transduction; Tumor Suppression; experience; glutathione peroxidase; oxidative damage; repair enzyme; repaired; small molecule; translational potential; tumor

Ferroptosis in a new form of regulated, non-apoptotic cell death that we discovered; we have determined the major mechanisms regulating activation of ferroptosis and several contexts where it can be induced in sensitized tumors. We found that ferroptosis is ultimately characterized by excessive lipid peroxidation upon loss of activity of the lipid repair enzyme glutathione peroxidase 4 (Gpx4). We propose here the hypothesis that lipid peroxidation serves as a signal to detect a scarcity of nutrients needed tor repair of oxidative damage, and that ferroptosis serves as an innate tumor suppression mechanism to eliminate nascent tumors experiencing such oxidative stress. We further propose to elucidate mechanisms driving ferroptosis in specific cancer contexts, and whether it is feasible to create precision small molecule activators of ferroptosis that eliminate tumors that have become addicted to this repair pathway.

我们发现了一种新形式的受调控的非凋亡细胞死亡——铁死亡；我们 已经确定了调节铁死亡激活的主要机制和一些 它可以在致敏肿瘤中诱导的环境。我们发现铁死亡是 最终特征是脂质活性丧失后过度脂质过氧化 修复酶谷胱甘肽过氧化物酶 4 (Gpx4)。我们在此提出假设 脂质过氧化作为检测修复所需营养物质缺乏的信号 氧化损伤，铁死亡是一种先天性肿瘤抑制 消除经历这种氧化应激的新生肿瘤的机制。我们进一步 提议阐明在特定癌症背景下驱动铁死亡的机制，以及 是否可以制造精确的铁死亡小分子激活剂 消除对这种修复途径上瘾的肿瘤。

项目成果

Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis.

具有两个多不饱和脂肪酰基尾部的磷脂促进铁死亡。

• 发表时间: 2024-02-29
• 影响因子: 64.5
• 作者: Qiu, Baiyu;Zandkarimi, Fereshteh;Bezjian, Carla T;Reznik, Eduard;Soni, Rajesh Kumar;Gu, Wei;Jiang, Xuejun;Stockwell, Brent R
• 通讯作者: Stockwell, Brent R

Kinases Controlling Stability of the Oncogenic MYCN Protein.

控制致癌 MYCN 蛋白稳定性的激酶。

• 发表时间: 2023-12-14
• 影响因子: 4.2
• 作者: Smith, Nailah;Reznik, Eduard;Bisikirska, Brygida;Polychronidou, Vasiliki;Wang, Qian;Zask, Arie;Forouhar, Farhad;Califano, Andrea;Stockwell, Brent R
• 通讯作者: Stockwell, Brent R

Inhibition of neuronal ferroptosis protects hemorrhagic brain.

抑制神经元铁死亡可保护出血性脑。

• DOI: 10.1172/jci.insight.90777
• 发表时间: 2017-04-06
• 期刊: JCI insight
• 影响因子: 8
• 作者: Qian Li;Xiaoning Han;Xi Lan;Yufeng Gao;Jie;Frederick Durham;Tian Cheng;Jie Yang;Zhong
• 通讯作者: Zhong

Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis.

脂氧合酶对多不饱和脂肪酸的过氧化会导致铁死亡。

• 发表时间: 2016-08-23
• 影响因子: 11.1
• 作者: Yang, Wan Seok;Kim, Katherine J;Gaschler, Michael M;Patel, Milesh;Shchepinov, Mikhail S;Stockwell, Brent R
• 通讯作者: Stockwell, Brent R

Heat stress induces ferroptosis-like cell death in plants.

热应激会诱导植物中类似铁死亡的细胞死亡。

• 发表时间: 2017-02
• 作者: Distéfano, Ayelén Mariana;Martin, María Victoria;Córdoba, Juan Pablo;Bellido, Andrés Martín;D'Ippólito, Sebastián;Colman, Silvana Lorena;Soto, Débora;Roldán, Juan Alfredo;Bartoli, Carlos Guillermo;Zabaleta, Eduardo Julián;Fiol, Diego Fernando;S
• 通讯作者: S