Ferroptosis: quá khứ, hiện tại và tương lai
Tóm tắt
Ferroptosis là một loại cell chết mới được phát hiện trong những năm gần đây, thường đi kèm với sự tích lũy một lượng lớn sắt và sự peroxid hóa lipid trong quá trình chết tế bào; sự xảy ra của ferroptosis phụ thuộc vào sắt. Các yếu tố kích thích ferroptosis có thể ảnh hưởng trực tiếp hoặc gián tiếp đến glutathione peroxidase thông qua các con đường khác nhau, dẫn đến sự giảm khả năng chống oxy hóa và sự tích lũy các loài oxy phản ứng (ROS) lipit trong tế bào, cuối cùng dẫn đến cái chết tế bào do oxy hóa. Các nghiên cứu gần đây đã chỉ ra rằng ferroptosis có liên quan mật thiết đến các quá trình bệnh sinh của nhiều bệnh, như khối u, bệnh lý hệ thần kinh, tổn thương thiếu máu - tái tưới máu, tổn thương thận và bệnh máu. Cách can thiệp vào sự xuất hiện và phát triển của các bệnh liên quan bằng cách điều chỉnh ferroptosis của tế bào đã trở thành một điểm nóng và trọng tâm của nghiên cứu và điều trị nguyên nhân, nhưng các thay đổi chức năng và các cơ chế phân tử cụ thể của ferroptosis vẫn cần được khám phá thêm. Bài báo này tóm tắt có hệ thống những tiến bộ mới nhất trong nghiên cứu ferroptosis, với mục tiêu cung cấp tài liệu tham khảo để hiểu sâu hơn về nguyên nhân bệnh và đề xuất các mục tiêu mới cho việc điều trị các bệnh liên quan.
Từ khóa
Tài liệu tham khảo
Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).
Yang, W. S. & Stockwell, B. R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 15, 234–245 (2008).
Yagoda, N. et al. RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447, 864–868 (2007).
Dolma, S., Lessnick, S. L., Hahn, W. C. & Stockwell, B. R. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3, 285–296 (2003).
Friedmann Angeli, J. P. et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 16, 1180–1191 (2014).
Wu, Z. et al. Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc. Natl Acad. Sci. USA 116, 2996–3005 (2019).
Liang, C., Zhang, X., Yang, M. & Dong, X. Recent progress in ferroptosis inducers for cancer therapy. Adv. Mater. Weinh. 31, 1904197 (2019).
Skouta, R. et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J. Am. Chem. Soc. 136, 4551–4556 (2014).
Jiang, L., Hickman, J. H., Wang, S. J. & Gu, W. Dynamic roles of p53‐mediated metabolic activities in ROS‐induced stress responses. Cell Cycle 14, 2881–5 (2015).
Jiang, L. et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520, 57–62 (2015).
Warner, G. J. et al. Inhibition of selenoprotein synthesis by selenocysteine tRNA [Ser]Sec lacking isopentenyladenosine. J. Biol. Chem. 275, 28110–9 (2000).
Skonieczna, M. et al. The impact of DIDS-induced inhibition of voltage-dependent anion channels (VDAC) on cellular response of lymphoblastoid cells to ionizing radiation. Med Chem. 13, 477–483 (2017).
Ou, Y., Wang, S. J., Li, D., Chu, B. & Gu, W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc. Natl Acad. Sci. USA 113, E6806–E6812 (2016).
Tarangelo, A. et al. p53 suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Rep. 22, 569–575 (2018).
Xie, Y. et al. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep. 20, 1692–1704 (2017).
Bersuker, K. et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692 (2019).
Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698 (2019).
Susin, S. A. et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, 441–446 (1999).
Wu, M., Xu, L. G., Li, X., Zhai, Z. & Shu, H. B. AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis. J. Biol. Chem. 277, 25617–25623 (2002).
Bogdan, A. R., Miyazawa, M., Hashimoto, K. & Tsuji, Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 41, 274–286 (2016).
Gao, M., Monian, P., Quadri, N., Ramasamy, R. & Jiang, X. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59, 298–308 (2015).
Kwon, M. Y., Park, E., Lee, S. J. & Chung, S. W. Heme oxygenase-1 accelerates erastin‐induced ferroptotic cell death. Oncotarget 6, 24393–24403. (2015).
Sun, X. et al. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34, 5617–25 (2015).
Gammella, E., Recalcati, S., Rybinska, I., Buratti, P. & Cairo, G. Iron-induced damage in cardiomyopathy: oxidative-dependent and independent mechanisms. Oxid. Med Cell Longev. 2015, 230182 (2015).
Yang, W. S. & Stockwell, B. R. Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 26, 165–176 (2016).
Kagan, V. E. et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13, 81–90 (2017).
McBean, G. J. The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino acids 42, 199–205 (2012).
Sun, X. et al. Activation of the p62-Keapl-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 63, 173–184 (2016).
Hou, W. et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12, 1425–1428 (2016).
Eling, N., Reuter, L., Hazin, J., Hamacher-Brady, A. & Brady, N. R. Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2, 517–532 (2015).
Yamaguchi, Y., Kasukabe, T. & Kumakura, S. Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. Int J. Oncol. 52, 1011–1022 (2018).
Louandre, C. et al. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells. Cancer Lett. 356, 971–977 (2015).
Ou, W. et al. Low-density lipoprotein docosahexaenoic acid nanoparticles induce ferroptotic cell death in hepatocellular carcinoma. Free Radic. Biol. Med 112, 597–607 (2017).
Bai, T. et al. Sigma-1 receptor protects against ferroptosis in hepatocellular carcinoma cells. J. Cell Mol. Med 23, 7349–7359 (2019).
Bai, T. et al. Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells. Biochem Biophys. Res Commun. 491, 919–925 (2017).
Nie, J., Lin, B., Zhou, M., Wu, L. & Zheng, T. Role of ferroptosis in hepatocellular carcinoma. J. Cancer Res Clin. Oncol. 144, 2329–37. (2018).
Sun, X. et al. Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology 64, 488–500 (2016).
Yuan, H., Li, X., Zhang, X., Kang, R. & Tang, D. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys. Res Commun. 478, 838–844 (2016).
Hao, S. et al. Cysteine dioxygenase 1 mediates erastin-induced ferroptosis in human gastric cancer cells. Neoplasia 19, 1022–1032 (2017).
Guo, J. et al. Ferroptosis: a novel anti-tumor action for cisplatin. Cancer Res Treat. 50, 445–460 (2018).
Chen, M. S. et al. CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2alpha-ATF4 pathway. Oncotarget 8, 114588–114602 (2017).
Masanori, H. et al. Functional interactions of the cystine/glutamate antiporter, CD44v and MUC1-C oncoprotein in triple-negative breast cancer cells. Oncotarget 7, 11756–11769 (2016).
Ishimoto, T. et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc and thereby promotes tumor growth. Cancer Cell 19, 387–400 (2011).
Alvarez, S. W. et al. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 551, 639–643 (2017).
Miess, H. et al. The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma. Oncogene 37, 5435–5450 (2018).
Belavgeni, A. et al. Exquisite sensitivity of adrenocortical carcinomas to induction of ferroptosis. Proc. Natl Acad. Sci. USA 116, 22269–22274 (2019).
Greenshields, A. L., Shepherd, T. G. & Hoskin, D. W. Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Mol. Carcinog. 56, 75–93 (2016).
Basuli, D. et al. Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene 36, 4089–4099 (2017).
Luo, M. et al. miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma. Cell Death Differ. 25, 1457–1472 (2018).
Basit, F. et al. Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis. 8, e2716 (2017).
Kim, S. E. et al. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol. 11, 977–985 (2016).
Shin, D., Kim, E. H., Lee, J. & Roh, J. L. Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic. Biol. Med 129, 454–462 (2018).
Roh, J. L., Kim, E. H., Jang, H. & Shin, D. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol. 11, 254–262 (2017).
Kim, E. H., Shin, D., Lee, J., Jung, A. R. & Roh, J. L. CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer Lett. 432, 180–190 (2018).
Raven, E. P., Lu, P. H., Tishler, T. A., Heydari, P. & Bartzokis, G. Increased iron levels and decreased tissue integrity in hippocampus of Alzheimer’s disease detected in vivo with magnetic resonance imaging. J. Alzheimers Dis. 37, 127–136 (2013).
Lane, D. J. R., Ayton, S. & Bush, A. I. Iron and Alzheimer’s disease: an update on emerging mechanisms. J. Alzheimers Dis. 64, S379–S395 (2018).
Hambright, W. S., Fonseca, R. S., Chen, L., Na, R. & Ran, Q. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol. 12, 8–17 (2017).
Ayton, S. & Lei, P. Nigral iron elevation is an invariable feature of Parkinson’s disease and is a sufficient cause of neurodegeneration. Biomed. Res Int 2014, 581256 (2014).
Do Van, B. et al. Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC. Neurobiol. Dis. 94, 169–178 (2016).
Agrawal, S., Fox, J., Thyagarajan, B. & Fox, J. H. Brain mitochondrial iron accumulates in Huntington’s disease, mediates mitochondrial dysfunction, and can be removed pharmacologically. Free Radic. Biol. Med 120, 317–329 (2018).
Klepac, N. et al. Oxidative stress parameters in plasma of Huntington’s disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects: a cross-sectional study. J. Neurol. 254, 1676–1683 (2007).
Chen, J. et al. Iron accumulates in Huntington’s disease neurons: protection by deferoxamine. PLoS ONE 8, e77023 (2013).
Kwan, J. Y. et al. Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. PLoS ONE 7, e35241 (2012).
Johnson, W. M., Wilson-Delfosse, A. L. & Mieyal, J. J. Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients 4, 1399–1440 (2012).
Codazzi, F. et al. Friedreich ataxia-induced pluripotent stem cell-derived neurons show a cellular phenotype that is corrected by a benzamide HDAC inhibitor. Hum. Mol. Genet 25, 4847–4855 (2016).
Dietrich, R. B. & Bradley, W. G. Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children. Radiology 168, 203–206 (1988).
Ahmad, S. et al. Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke. Neurotoxicology 45, 100–110 (2014).
Hanson, L. R. et al. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J. Pharm. Exp. Ther. 330, 679–686 (2009).
Karuppagounder, S. S. et al. N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with prostaglandin E2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice. Ann. Neurol. 84, 854–872 (2018).
Zhang, Z. et al. Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage. Brain Res 1701, 112–125 (2018).
Xie, B. S. et al. Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice. CNS Neurosci. Ther. 25, 465–475 (2019).
Friedmann Angeli, J. P. et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 16, 1180–1191 (2014).
Linkermann, A. et al. Synchronized renal tubular cell death involves ferroptosis. Proc. Natl Acad. Sci. USA 111, 16836–16841 (2014).
Martin-Sanchez, D. et al. Ferroptosis, but not necroptosis, is important in nephrotoxic folic acid-induced AKI. J. Am. Soc. Nephrol. 28, 218–229 (2017).
Adedoyin, O. et al. Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. Am. J. Physiol. Ren. Physiol. 314, F702–F714 (2018).
Li, W. & Feng, G. et al. Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation. J. Clin. Invest 129, 2293–2304 (2019).
Fang, X. et al. Ferroptosis as a target for protection against cardiomyopathy. Proc. Natl Acad. Sci. USA 116, 2672–2680 (2019).
Wang, L. et al. P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation. IUBMB Life 71, 45–56 (2019).
Bruni, A. et al. Ferroptosis-inducing agents compromise in vitro human islet viability and function. Cell Death Dis. 9, 595 (2018).
Yu, Y. et al. The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol. Cell Oncol. 2, e1054549 (2015).
Sun, Y., Zheng, Y., Wang, C. & Liu, Y. Glutathione depletion induces ferroptosis, autophagy, and premature cell senescence in retinal pigment epithelial cells. Cell Death Dis. 9, 753 (2018).
Arbiser, J. L., Bonner, M. Y., Ward, N., Elsey, J. & Rao, S. Selenium unmasks protective iron armor: a possible defense against cutaneous inflammation and cancer. Biochim Biophys. Acta Gen. Subj. 1862, 2518–2527 (2018).
NaveenKumar, S. K. et al. The role of reactive oxygen species and ferroptosis in heme-mediated activation of human platelets. ACS Chem. Biol. 13, 1996–2002 (2018).
von Mässenhausen, A., Tonnus, W. & Linkermann, A. Cell death pathways drive necroinflammation during acute kidney injury. Nephron 140, 144–147 (2018).
Li, C. et al. Activation of glutathione peroxidase 4 as a novel anti-inflammatory strategy. Front Pharm. 9, 1120 (2018).
Maher, P. Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: implications for age-related neurodegenerative diseases. Free Radic. Biol. Med 115, 92–104 (2017).