Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death.
Ionizing radiation results in a mixture of cellular outcomes including mitotic catastrophe, senescence, methuosis, and iron-dependent cell death.
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DOI：
10.1038/s41419-020-03209-y
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发表时间：
2020-11-23
影响因子：
9
通讯作者：
Vandenabeele P
中科院分区：
文献类型：
--
作者：
Adjemian S;Oltean T;Martens S;Wiernicki B;Goossens V;Vanden Berghe T;Cappe B;Ladik M;Riquet FB;Heyndrickx L;Bridelance J;Vuylsteke M;Vandecasteele K;Vandenabeele P
放射治疗通常被用作多种肿瘤的细胞毒性治疗。有趣的是，很少有病例报告强调其诱导免疫介导的体外效应的潜力，导致远离照射部位的转移灶的消退。这些观察是罕见的，显然取决于所使用的剂量，这表明剂量相关的细胞反应可能参与远端免疫原性反应。据报道，电离辐射（IR）可引起免疫原性细胞凋亡、坏死下垂、有丝分裂突变和衰老。为了将细胞结果与特定剂量的辐射联系起来，我们对一组细胞系在不同剂量的x射线下的细胞反应进行了系统的研究。值得注意的是，我们观察到所有被测试的细胞系都以类似的方式响应IR，具有有丝分裂突变、衰老、脂质过氧化和半胱天冬酶活性的特征。铁螯合剂（但不包括铁抑素-1或维生素E）可以阻止脂质过氧化物的形成和IR诱导的细胞死亡，提示高剂量辐照下铁依赖性细胞死亡的关键作用。我们还表明，在K-Ras突变的细胞中，IR可以诱导类似于methuosis的形态学特征，这是最近在H-Ras或K-Ras突变过表达后描述的一种细胞死亡模式。
Radiotherapy is commonly used as a cytotoxic treatment of a wide variety of tumors. Interestingly, few case reports underlined its potential to induce immune-mediated abscopal effects, resulting in regression of metastases, distant from the irradiated site. These observations are rare, and apparently depend on the dose used, suggesting that dose-related cellular responses may be involved in the distant immunogenic responses. Ionizing radiation (IR) has been reported to elicit immunogenic apoptosis, necroptosis, mitotic catastrophe, and senescence. In order to link a cellular outcome with a particular dose of irradiation, we performed a systematic study in a panel of cell lines on the cellular responses at different doses of X-rays. Remarkably, we observed that all cell lines tested responded in a similar fashion to IR with characteristics of mitotic catastrophe, senescence, lipid peroxidation, and caspase activity. Iron chelators (but not Ferrostatin-1 or vitamin E) could prevent the formation of lipid peroxides and cell death induced by IR, suggesting a crucial role of iron-dependent cell death during high-dose irradiation. We also show that in K-Ras-mutated cells, IR can induce morphological features reminiscent of methuosis, a cell death modality that has been recently described following H-Ras or K-Ras mutation overexpression.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3
作者：
Dimauro T;David G
通讯作者：
David G
DOI：
10.1073/pnas.0409130102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Huang, XX;Tran, T;Zhang, PM
通讯作者：
Zhang, PM
DOI：
10.1083/jcb.136.1.215
发表时间：
1997-01-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy NJ;Whyte MK;Gilbert CS;Evan GI
通讯作者：
Evan GI