靶向铁死亡防治重大疾病研究进展
Research Progress on Targeting Ferroptosis to Prevent and Treat Major Diseases
摘要: 铁死亡(Ferroptosis)是一种铁依赖的细胞死亡途径，其特征在于引起脂质过氧化物的积聚，同时过量Fe2 通过芬顿反应(Fenton reaction)氧化细胞膜上不饱和脂肪酸(polyunsaturated fatty acids, PUFAs)，从而引发铁死亡。已经有报道铁死亡在包括肿瘤、心血管疾病、肝脏疾病等重大疾病中发挥重要的防治作用。本综述总结了铁死亡在肿瘤、心血管疾病、肝脏疾病以及其他疾病中的最新研究进展，并探讨了铁死亡在防治重大疾病中的前景，为防治重大疾病提供新的策略。
Abstract: Ferroptosis is an iron-dependent cell death mode, characterized by the accumulation of lipid peroxides and the oxidation of polyunsaturated fatty acids (PUFAs) on the cell membrane by excessive Fe2 through the Fenton reaction, leading to ferroptosis. It has been reported that ferroptosis plays an important role in the prevention and treatment of major diseases, including tumors, cardiovascular diseases, liver diseases and so on. This review summarizes the latest research progress of ferroptosis in tumors, cardiovascular diseases, liver diseases and other diseases, and discusses the prospect of ferroptosis in the prevention and treatment of major diseases, so as to provide new strategies for the prevention and treatment of major diseases.
文章引用：刘耀东. 靶向铁死亡防治重大疾病研究进展[J]. 临床医学进展, 2024, 14(4): 2037-2044. https://doi.org/10.12677/acm.2024.1441260

参考文献

[1] Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., et al. (2012) Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell, 149, 1060-1072. [Google Scholar] [CrossRef] [PubMed]
[2] Zheng, J. and Conrad, M. (2020) The Metabolic Underpinnings of Ferroptosis. Cell Metabolism, 32, 920-937. [Google Scholar] [CrossRef] [PubMed]
[3] Stockwell, B.R., Friedmann Angeli, J.P., Bayir, H., et al. (2017) Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell, 171, 273-285. [Google Scholar] [CrossRef] [PubMed]
[4] Yang, W.S., SriRamaratnam, R., Welsch, M.E., et al. (2014) Regulation of Ferroptotic Cancer Cell Death by GPX4. Cell, 156, 317-331. [Google Scholar] [CrossRef] [PubMed]
[5] Yang, W.S. and Stockwell, B.R. (2016) Ferroptosis: Death by Lipid Peroxidation. Trends in Cell Biology, 26, 165-176. [Google Scholar] [CrossRef] [PubMed]
[6] Xie, Y., Kang, R., Klionsky, D.J., et al. (2023) GPX4 in Cell Death, Autophagy, and Disease. Autophagy, 19, 2621-2638. [Google Scholar] [CrossRef] [PubMed]
[7] Kraft, V.A.N., Bezjian, C.T., Pfeiffer, S., et al. (2020) GTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis Through Lipid Remodeling. ACS Central Science, 6, 41-53. [Google Scholar] [CrossRef] [PubMed]
[8] Doll, S., Freitas, F.P., Shah, R., et al. (2019) FSP1 Is a Glutathione-Independent Ferroptosis Suppressor. Nature, 575, 693-698. [Google Scholar] [CrossRef] [PubMed]
[9] Yang, M., Tsui, M.G., Tsang, J.K.W., et al. (2022) Involvement of FSP1-CoQ-NADH and GSH-GPx-4 Pathways in Retinal Pigment Epithelium Ferroptosis. Cell Death & Disease, 13, Article No. 468. [Google Scholar] [CrossRef] [PubMed]
[10] Bersuker, K., Hendricks, J.M., Li, Z., et al. (2019) The CoQ Oxidoreductase FSP1 Acts Parallel to GPX4 to Inhibit Ferroptosis. Nature, 575, 688-692. [Google Scholar] [CrossRef] [PubMed]
[11] Li, W., Liang, L., Liu, S., et al. (2023) FSP1: A Key Regulator of Ferroptosis. Trends in Molecular Medicine, 29, 753-764. [Google Scholar] [CrossRef] [PubMed]
[12] Doll, S., Proneth, B., Tyurina, Y.Y., et al. (2017) ACSL4 Dictates Ferroptosis Sensitivity by Shaping Cellular Lipid Composition. Nature Chemical Biology, 13, 91-98. [Google Scholar] [CrossRef] [PubMed]
[13] Bai, Y., Meng, L., Han, L., et al. (2019) Lipid Storage and Lipophagy Regulates Ferroptosis. Biochemical and Biophysical Research Communications, 508, 997-1003. [Google Scholar] [CrossRef] [PubMed]
[14] Kagan, V.E., Mao, G., Qu, F., et al. (2017) Oxidized Arachidonic and Adrenic PEs Navigate Cells to Ferroptosis. Nature Chemical Biology, 13, 81-90. [Google Scholar] [CrossRef] [PubMed]
[15] Wenzel, S.E., Tyurina, Y.Y., Zhao, J., et al. (2017) PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell, 171, 628-641.E26. [Google Scholar] [CrossRef] [PubMed]
[16] Hangauer, M.J., Viswanathan, V.S., Ryan, M.J., et al. (2017) Drug-Tolerant Persister Cancer Cells Are Vulnerable to GPX4 Inhibition. Nature, 551, 247-250. [Google Scholar] [CrossRef] [PubMed]
[17] Hassannia, B., Vandenabeele, P., Vanden Berghe, T. et al. (2019) Targeting Ferroptosis to Iron out Cancer. Cancer Cell, 35, 830-849. [Google Scholar] [CrossRef] [PubMed]
[18] Hu, K., Li, K., Lv, J., et al. (2020) Suppression of the SLC7A11/Glutathione Axis Causes Synthetic Lethality in KRAS-Mutant Lung Adenocarcinoma. Journal of Clinical Investigation, 130, 1752-1766. [Google Scholar] [CrossRef] 
[19] Chen, X., Kang, R., Kroemer, G. and Tang. D. (2021) Broadening Horizons: The Role of Ferroptosis in Cancer. Nature Reviews Clinical Oncology, 18, 280-296. [Google Scholar] [CrossRef] [PubMed]
[20] Garwood, E.R., Kumar, A.S., Baehner, F.L., et al. (2010) Fluvastatin Reduces Proliferation and Increases Apoptosis in Women with High Grade Breast Cancer. Breast Cancer Research and Treatment, 119, 137-144. [Google Scholar] [CrossRef] [PubMed]
[21] Gout, P.W., Buckley, A.R., Simms, C.R. and Bruchovsky, N. (2001) Sulfasalazine, A Potent Suppressor of Lymphoma Growth by Inhibition of the XC- Cystine Transporter: A New Action for an Old Drug. Leukemia, 15, 1633-1640. [Google Scholar] [CrossRef] [PubMed]
[22] Graf, H., Jüngst, C., Straub, G., et al. (2008) Chemoembolization Combined with Pravastatin Improves Survival in Patients with Hepatocellular Carcinoma. Digestion, 78, 34-38. [Google Scholar] [CrossRef] [PubMed]
[23] Hus, M., Grzasko, N., Szostek, M., et al. (2011) Thalidomide, Dexamethasone and Lovastatin with Autologous Stem Cell Transplantation as a Salvage Immunomodulatory Therapy in Patients with Relapsed and Refractory Multiple Myeloma. Annals of Hematology, 90, 1161-1166. [Google Scholar] [CrossRef] [PubMed]
[24] Li, J. and Zhou, B. (2010) Biological Actions of Artemisinin: Insights from Medicinal Chemistry Studies. Molecules, 15, 1378-1397. [Google Scholar] [CrossRef] [PubMed]
[25] Louandre, C., Ezzoukhry, Z., Godin, C., et al. (2013) Iron-Dependent Cell Death of Hepatocellular Carcinoma Cells Exposed to Sorafenib. International Journal of Cancer, 133, 1732-1742. [Google Scholar] [CrossRef] [PubMed]
[26] Stockwin, L.H., Han, B., Yu, S.X., et al. (2009) Artemisinin Dimer Anticancer Activity Correlates with Heme-Catalyzed Reactive Oxygen Species Generation and Endoplasmic Reticulum Stress Induction. International Journal of Cancer, 125, 1266-1275. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, Y., Tan, H., Daniels, J.D., et al. (2019) Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model. Cell Chemical Biology, 26, 623-633.E9. [Google Scholar] [CrossRef] [PubMed]
[28] Kim, S.E., Zhang, L., Ma, K., et al. (2016) Ultrasmall Nanoparticles Induce Ferroptosis in Nutrient-Deprived Cancer Cells and Suppress Tumour Growth. Nature Nanotechnology, 11, 977-985. [Google Scholar] [CrossRef] [PubMed]
[29] Bjarnadottir, O., Romero, Q., Bendahl, P.O., et al. (2013) Targeting HMG-CoA Reductase with Statins in a Window-of-Opportunity Breast Cancer Trial. Breast Cancer Research and Treatment, 138, 499-508. [Google Scholar] [CrossRef] [PubMed]
[30] Yang, Y., Sun, B., Zuo, S., et al. (2020) Trisulfide Bond-Mediated Doxorubicin Dimeric Prodrug Nanoassemblies with High Drug Loading, High Self-Assembly Stability, and High Tumor Selectivity. Science Advances, 6, eabc1725. [Google Scholar] [CrossRef] [PubMed]
[31] Yang, Y.X., Zuo, S., Zhang, J.X., et al. (2022) Prodrug Nanoassemblies Bridged by Mono-/Di-/Tri-Sulfide Bonds: Exploration Is for Going Further. Nano Today, 44, Article ID: 101480. [Google Scholar] [CrossRef] 
[32] Chen, G., Yang, Y., Xu, Q., et al. (2020) Self-Amplification of Tumor Oxidative Stress with Degradable Metallic Complexes for Synergistic Cascade Tumor Therapy. Nano Letters, 20, 8141-8150. [Google Scholar] [CrossRef] [PubMed]
[33] Zhou, L. and Dong, C. (2021) Targeting Ferroptosis Synergistically Sensitizes Apoptotic Sonodynamic Anti-Tumor Nanotherapy. Nano Today, 39, Article ID: 101212. [Google Scholar] [CrossRef] 
[34] Chen, Q., Ma, X., Xie, L., et al. (2021) Iron-Based Nanoparticles for MR Imaging-Guided Ferroptosis in Combination with Photodynamic Therapy to Enhance Cancer Treatment. Nanoscale, 13, 4855-4870. [Google Scholar] [CrossRef] 
[35] Zhao, Y., Li, M., Yao, X., et al. (2020) HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications. Cell Reports, 33, Article ID: 108487. [Google Scholar] [CrossRef] [PubMed]
[36] Chen, J., Li, X., Ge, C., Min, J. and Wang, F. (2022) The Multifaceted Role of Ferroptosis in Liver Disease. Cell Death & Differentiation, 29, 467-480. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, H., An, P., Xie, E., et al. (2017) Characterization of Ferroptosis in Murine Models of Hemochromatosis. Hepatology, 66, 449-465. [Google Scholar] [CrossRef] [PubMed]
[38] Fang, X., Zhang, J., Li, Y., et al. (2023) Malic Enzyme 1 as a Novel Anti-Ferroptotic Regulator in Hepatic Ischemia/Reperfusion Injury. Advanced Science, 10, e2205436. [Google Scholar] [CrossRef] [PubMed]
[39] Meng, H., Yu, Y., Xie, E., et al. (2023) Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway. Research, 6, Article 0281. [Google Scholar] [CrossRef] [PubMed]
[40] Guo, J., Duan, L., He, X., et al. (2021) A Combined Model of Human IPSC-Derived Liver Organoids and Hepatocytes Reveals Ferroptosis in DGUOK Mutant MtDNA Depletion Syndrome. Advanced Science, 8, Article ID: 2004680. [Google Scholar] [CrossRef] [PubMed]
[41] Wu, Y., Jiao, H., Yue, Y., et al. 2022) Ubiquitin Ligase E3 HUWE1/MULE Targets Transferrin Receptor for Degradation and Suppresses Ferroptosis in Acute Liver Injury. Cell Death & Differentiation, 29, 1705-1718.
[42] Fang, X., Wang, H., Han, D., et al. (2022) Ferroptosis as a Target for Protection against Cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 116, 2672-2680. [Google Scholar] [CrossRef] [PubMed]
[43] Ta, N., Qu, C., Wu, H., et al. (2022) Mitochondrial Outer Membrane Protein FUNDC2 Promotes Ferroptosis and Contributes to Doxorubicin-Induced Cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America, 119, e2117396119. [Google Scholar] [CrossRef] [PubMed]
[44] Gao, M., Monian, P., Quadri, N., et al. (2015) Glutaminolysis and Transferrin Regulate Ferroptosis. Molecular Cell, 59, 298-308. [Google Scholar] [CrossRef] [PubMed]
[45] Stamenkovic, A., Pierce, G.N. and Ravandi, A. (2019) Phospholipid Oxidation Products in Ferroptotic Myocardial Cell Death. American Journal of Physiology-Heart and Circulatory Physiology, 317, H156-H163. [Google Scholar] [CrossRef] [PubMed]
[46] Menon, A.V., Liu, J., Tsai, H.P., et al. (2022) Excess Heme Upregulates Heme Oxygenase 1 and Promotes Cardiac Ferroptosis in Mice with Sickle Cell Disease. Blood, 139, 936-941. [Google Scholar] [CrossRef] [PubMed]
[47] Li, J., Pan, X., Pan, G., et al. (2020) Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/ Beige Adipocytes. Advanced Science, 7, Article ID: 1903366. [Google Scholar] [CrossRef] 
[48] Yang, L., Wang, H., Yang, X., et al. (2020) Auranofin Mitigates Systemic Iron Overload and Induces Ferroptosis via Distinct Mechanisms. Signal Transduction and Targeted Therapy, 5, Article No. 138. [Google Scholar] [CrossRef] [PubMed]
[49] Von Mässenhausen, A., Zamora Gonzalez, N., Maremonti, F., et al. (2022) Dexamethasone Sensitizes to Ferroptosis by Glucocorticoid Receptor-Induced Dipeptidase-1 Expression and Glutathione Depletion. Science Advances, 8, eabl8920. [Google Scholar] [CrossRef] [PubMed]
[50] Rui, T., Wang, H., Li, Q., et al. (2021) Deletion of Ferritin H in Neurons Counteracts the Protective Effect of Melatonin against Traumatic Brain Injury-Induced Ferroptosis. Journal of Pineal Research, 70, e12704. [Google Scholar] [CrossRef] [PubMed]
[51] Hu, Q., Zhang, Y., Lou, H., et al. (2021) GPX4 and Vitamin E Cooperatively Protect Hematopoietic Stem and Progenitor Cells from Lipid Peroxidation and Ferroptosis. Cell Death & Disease, 12, Article No. 706. [Google Scholar] [CrossRef] [PubMed]
[52] Tu, L.F., Zhang, T.Z., Zhou, Y.F., et al. (2023) GPX4 Deficiency-Dependent Phospholipid Peroxidation Drives Motor Deficits of ALS. Journal of Advanced Research, 43, 205-218. [Google Scholar] [CrossRef] [PubMed]

为你推荐