Nrf2在暴露于电离辐射后可促进细胞存活。
Nrf2 promotes survival following exposure to ionizing radiation.
作者信息
Sekhar Konjeti R, Freeman Michael L
机构信息
Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
出版信息
Free Radic Biol Med. 2015 Nov;88(Pt B):268-274. doi: 10.1016/j.freeradbiomed.2015.04.035. Epub 2015 May 12.
Abstract
Nrf2 is a transcription factor that promotes antioxidant and drug-metabolizing gene expression. It also regulates the transcription of genes involved in carbohydrate and lipid metabolism, NADPH regeneration, and heme and iron metabolism, as well as proteasome metabolism. Emerging research has identified Nrf2 as a critical factor for promoting survival of mammalian cells subjected to ionizing radiation. At a mechanistic level, Nrf2 promotes the repair of DNA damage and drives detoxification of superoxide that is generated hours to days after irradiation. This review summarizes research in these areas and discusses targeting of Nrf2 in radiation-resistant cancer and Nrf2׳s role in mitigating acute radiation syndrome.
摘要
Nrf2是一种促进抗氧化和药物代谢基因表达的转录因子。它还调节参与碳水化合物和脂质代谢、NADPH再生、血红素和铁代谢以及蛋白酶体代谢的基因的转录。新出现的研究已将Nrf2确定为促进受电离辐射的哺乳动物细胞存活的关键因素。在机制层面，Nrf2促进DNA损伤的修复，并驱动辐射后数小时至数天产生的超氧化物的解毒。本综述总结了这些领域的研究，并讨论了在抗辐射癌症中靶向Nrf2以及Nrf2在减轻急性放射综合征中的作用。
相似文献
1
Nrf2 promotes survival following exposure to ionizing radiation.Nrf2在暴露于电离辐射后可促进细胞存活。
Free Radic Biol Med. 2015 Nov;88(Pt B):268-274. doi: 10.1016/j.freeradbiomed.2015.04.035. Epub 2015 May 12.
2
The Role of Nrf2 in the Response to Normal Tissue Radiation Injury.Nrf2 在正常组织辐射损伤反应中的作用。
Radiat Res. 2018 Aug;190(2):99-106. doi: 10.1667/RR15059.1. Epub 2018 May 25.
3
Response of the Nrf2 protection system in human monocytic cells after ionising irradiation.电离辐射后人类单核细胞中Nrf2保护系统的反应。
Radiat Prot Dosimetry. 2012 Nov;152(1-3):104-8. doi: 10.1093/rpd/ncs201. Epub 2012 Aug 31.
4
An effective strategy for increasing the radiosensitivity of Human lung Cancer cells by blocking Nrf2-dependent antioxidant responses.通过阻断 Nrf2 依赖性抗氧化反应来提高人肺癌细胞放射敏感性的有效策略。
Free Radic Biol Med. 2012 Aug 15;53(4):807-16. doi: 10.1016/j.freeradbiomed.2012.05.038. Epub 2012 Jun 7.
5
Nrf2 inhibition sensitizes breast cancer stem cells to ionizing radiation via suppressing DNA repair.Nrf2 抑制通过抑制 DNA 修复使乳腺癌干细胞对电离辐射敏感。
Free Radic Biol Med. 2021 Jun;169:238-247. doi: 10.1016/j.freeradbiomed.2021.04.006. Epub 2021 Apr 20.
6
Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.使用萝卜硫素反复刺激 Nrf2 可保护成纤维细胞免受电离辐射。
Toxicol Appl Pharmacol. 2014 May 1;276(3):188-94. doi: 10.1016/j.taap.2014.02.013. Epub 2014 Mar 3.
7
Brusatol Enhances the Radiosensitivity of A549 Cells by Promoting ROS Production and Enhancing DNA Damage.补骨脂酚通过促进活性氧生成和增强DNA损伤来提高A549细胞的放射敏感性。
Int J Mol Sci. 2016 Jun 24;17(7):997. doi: 10.3390/ijms17070997.
8
NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts.NRF2/miR-140信号通路赋予人肺成纤维细胞辐射防护作用。
Cancer Lett. 2015 Dec 1;369(1):184-91. doi: 10.1016/j.canlet.2015.08.011. Epub 2015 Aug 20.
9
Role of ionizing radiation activated NRF2 in lung cancer radioresistance.电离辐射激活 NRF2 在肺癌放射抵抗中的作用。
Int J Biol Macromol. 2023 Jun 30;241:124476. doi: 10.1016/j.ijbiomac.2023.124476. Epub 2023 Apr 17.
10
Nrf2 is a potential therapeutic target in radioresistance in human cancer.Nrf2 是人类癌症放射抵抗性的一个潜在治疗靶点。
Crit Rev Oncol Hematol. 2013 Dec;88(3):706-15. doi: 10.1016/j.critrevonc.2013.09.001. Epub 2013 Sep 29.
引用本文的文献
1
An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review.电离辐射通过激活NRF2途径增强正常干细胞增殖和分化作用的最新进展：综述
Antioxidants (Basel). 2025 Aug 11;14(8):986. doi: 10.3390/antiox14080986.
2
NRF2 pathway activation predicts poor prognosis in lung cancer: a cautionary note on antioxidant interventions.NRF2通路激活预示肺癌预后不良：关于抗氧化干预的警示
Geroscience. 2025 Jun 19. doi: 10.1007/s11357-025-01736-0.
3
Nrf2 Deficiency Brings About Increased Sensitive to IR and 7,12-dimethylbenz(a)anthracene and Leukemia Predisposition.Nrf2基因缺失导致对电离辐射和7,12-二甲基苯并(a)蒽敏感性增加及白血病易感性。
Dose Response. 2025 May 19;23(2):15593258251341593. doi: 10.1177/15593258251341593. eCollection 2025 Apr-Jun.
4
Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma.Nrf2：骨肉瘤放化疗耐药的关键调节因子。
Genes Dis. 2024 May 22;12(4):101335. doi: 10.1016/j.gendis.2024.101335. eCollection 2025 Jul.
5
Ferroptosis and noncoding RNAs: exploring mechanisms in lung cancer treatment.铁死亡与非编码RNA：探索肺癌治疗中的机制
Front Cell Dev Biol. 2025 Feb 26;13:1522873. doi: 10.3389/fcell.2025.1522873. eCollection 2025.
6
Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.利用正电子发射断层扫描成像非小细胞肺癌中的NRF2激活情况。
Nat Commun. 2024 Dec 17;15(1):10484. doi: 10.1038/s41467-024-54852-4.
7
A recombinant plasmid encoding human hepatocyte growth factor promotes healing of combined radiation-trauma skin injury involved in regulating Nrf2 pathway in mice.一种编码人肝细胞生长因子的重组质粒可促进小鼠放射性复合创伤皮肤损伤的愈合，其涉及调节 Nrf2 通路。
J Radiat Res. 2024 May 23;65(3):279-290. doi: 10.1093/jrr/rrae011.
8
Nrf-2 as a novel target in radiation induced lung injury.Nrf-2作为辐射诱导肺损伤的新靶点。
Heliyon. 2024 Apr 10;10(8):e29492. doi: 10.1016/j.heliyon.2024.e29492. eCollection 2024 Apr 30.
9
The combination of calreticulin-targeting L-ASNase and anti-PD-L1 antibody modulates the tumor immune microenvironment to synergistically enhance the antitumor efficacy of radiotherapy.钙网织蛋白靶向 L-天冬酰胺酶与抗 PD-L1 抗体联合调节肿瘤免疫微环境，协同增强放疗的抗肿瘤疗效。
Theranostics. 2024 Jan 20;14(3):1195-1211. doi: 10.7150/thno.90376. eCollection 2024.
10
Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.氧化应激和Nrf2信号通路在致病细胞和非致病细胞中的作用：一种可能的治疗抗性通用机制
Antioxidants (Basel). 2023 Jun 30;12(7):1371. doi: 10.3390/antiox12071371.
本文引用的文献
1
The many interactions between the innate immune system and the response to radiation.固有免疫系统与辐射反应之间的多种相互作用。
Cancer Lett. 2015 Nov 28;368(2):173-8. doi: 10.1016/j.canlet.2015.02.007. Epub 2015 Feb 11.
2
CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-甲酯（CDDO-Me）可保护正常肺和乳腺上皮细胞免受辐射，但对癌细胞无效。
PLoS One. 2014 Dec 23;9(12):e115600. doi: 10.1371/journal.pone.0115600. eCollection 2014.
3
Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity.碱基切除修复基因中的多态性：乳腺癌风险与个体辐射敏感性
World J Clin Oncol. 2014 Dec 10;5(5):874-82. doi: 10.5306/wjco.v5.i5.874.
4
Even free radicals should follow some rules: a guide to free radical research terminology and methodology.即使是自由基也应该遵循一些规则：自由基研究术语和方法学指南。
Free Radic Biol Med. 2015 Jan;78:233-5. doi: 10.1016/j.freeradbiomed.2014.10.504. Epub 2014 Oct 23.
5
Base excision repair capacity in informing healthspan.基础切除修复能力与健康寿命相关。
Carcinogenesis. 2014 Dec;35(12):2643-52. doi: 10.1093/carcin/bgu225. Epub 2014 Oct 29.
6
Apoptosis, necrosis, and autophagy in mouse intestinal damage after 15-Gy whole body irradiation.15 Gy全身照射后小鼠肠道损伤中的细胞凋亡、坏死和自噬
Cell Biochem Funct. 2014 Dec;32(8):647-56. doi: 10.1002/cbf.3068. Epub 2014 Oct 7.
7
Regulation of DNA pairing in homologous recombination.同源重组中DNA配对的调控。
Cold Spring Harb Perspect Biol. 2014 Sep 4;6(11):a017954. doi: 10.1101/cshperspect.a017954.
8
Quality control of homologous recombination.同源重组的质量控制。
Cell Mol Life Sci. 2014 Oct;71(19):3779-97. doi: 10.1007/s00018-014-1649-5. Epub 2014 May 25.
9
Nuclear factor E2-related factor-2 (Nrf2) is required for NLRP3 and AIM2 inflammasome activation.NLRP3和AIM2炎性小体激活需要核因子E2相关因子2（Nrf2）。
J Biol Chem. 2014 Jun 13;289(24):17020-9. doi: 10.1074/jbc.M114.563114. Epub 2014 May 5.
10
Inhibitory role of the KEAP1-NRF2 pathway in TGFβ1-stimulated renal epithelial transition to fibroblastic cells: a modulatory effect on SMAD signaling.KEAP1-NRF2通路在转化生长因子β1刺激的肾上皮细胞向成纤维细胞转变中的抑制作用：对SMAD信号传导的调节作用
PLoS One. 2014 Apr 1;9(4):e93265. doi: 10.1371/journal.pone.0093265. eCollection 2014.
Zotero 插件