Enlightening the Mechanism of Ferroptosis in Epileptic Heart


Cite item

Full Text

Abstract

Epilepsy is a chronic neurological degenerative disease with a high incidence, affecting all age groups. Refractory Epilepsy (RE) occurs in approximately 30-40% of cases with a higher risk of sudden unexpected death in epilepsy (SUDEP). Recent studies have shown that spontaneous seizures developed in epilepsy can be related to an increase in oxidative stress and reactive oxygen derivatives (ROS) production. Increasing ROS concentration causes lipid peroxidation, protein oxidation, destruction of nuclear genetic material, enzyme inhibition, and cell death by a mechanism known as "ferroptosis" (Fts). Inactivation of glutathione peroxidase 4 (GPX4) induces Fts, while oxidative stress is linked with increased intracellular free iron (Fe+2) concentration. Fts is also a non-apoptotic programmed cell death mechanism, where a hypoxia-inducible factor 1 alpha (HIF-1α) dependent hypoxic stress-like condition appears to occur with accumulation of iron and cytotoxic ROS in affected cells. Assuming convulsive crises as hypoxic stress, repetitive convulsive/hypoxic stress can be an effective inducer of the "epileptic heart" (EH), which is characterized by altered autonomic function and a high risk of malignant or fatal bradycardia. We previously reported that experimental recurrent seizures induce cardiomyocyte Fts associated with SUDEP. Furthermore, several genes related to Fts and hypoxia have recently been identified in acute myocardial infarction. An emerging theme from recent studies indicates that inhibition of GPX4 through modulating expression or activities of the xCT antiporter system (SLC7A11) governs cell sensitivity to oxidative stress from ferroptosis. Furthermore, during hypoxia, an increased expression of stress transcriptional factor ATF3 can promote Fts induced by erastin in a HIF-1α-dependent manner. We propose that inhibition of Fts with ROS scavengers, iron chelators, antioxidants, and transaminase inhibitors could provide a therapeutic effect in epilepsy and improve the prognosis of SUDEP risk by protecting the heart from ferroptosis.

About the authors

Enes Akyüz

Department of Biophysics, Faculty of International Medicine, University of Health Sciences

Email: info@benthamscience.net

Qamar Saleem

Faculty of International Medicine, University of Health Sciences

Email: info@benthamscience.net

Çiğdem Sari

Faculty of Medicine, Istanbul University

Email: info@benthamscience.net

Jerónimo Auzmendi

, National Council for Scientific and Technical Research (CONICET)

Email: info@benthamscience.net

Alberto Lazarowski

Clinical Biochemistry Department, Institute for Research in Physiopathology and Clinical Biochemistry (INFIBIOC), School of Pharmacy and Biochemistry,, University of Buenos Aires

Author for correspondence.
Email: info@benthamscience.net

References

  1. Stafstrom, C.E.; Carmant, L. Seizures and epilepsy: An overview for neuroscientists. Cold Spring Harb. Perspect. Med., 2015, 5(6), a022426. doi: 10.1101/cshperspect.a022426 PMID: 26033084
  2. Fazel, S.; Wolf, A.; Långström, N.; Newton, C.R.; Lichtenstein, P. Premature mortality in epilepsy and the role of psychiatric comorbidity: A total population study. Lancet, 2013, 382(9905), 1646-1654. doi: 10.1016/S0140-6736(13)60899-5 PMID: 23883699
  3. Devinsky, O.; Vezzani, A.; O’Brien, T.J.; Jette, N.; Scheffer, I.E.; de Curtis, M.; Perucca, P. Epilepsy. Nat. Rev. Dis. Primers, 2018, 4(1), 18024. doi: 10.1038/nrdp.2018.24 PMID: 29722352
  4. Hauser, W.; Hersdorffer, D. Epilepsy: Frequency, Causes and Consequences; Demos Medical Pub: New York, 1990.
  5. Beghi, E.; Giussani, G.; Sander, J.W. The natural history and prognosis of epilepsy. Epileptic Disord., 2015, 17(3), 243-253. doi: 10.1684/epd.2015.0751 PMID: 26234761
  6. Sen, A.; Jette, N.; Husain, M.; Sander, J.W. Epilepsy in older people. Lancet, 2020, 395(10225), 735-748. doi: 10.1016/S0140-6736(19)33064-8 PMID: 32113502
  7. Freitas, R.M.; Vasconcelos, S.M.M.; Souza, F.C.F.; Viana, G.S.B.; Fonteles, M.M.F. Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats. FEBS J., 2005, 272(6), 1307-1312. doi: 10.1111/j.1742-4658.2004.04537.x PMID: 15752349
  8. McElroy, P. B.; Liang, L. P.; Day, B. J.; Patel, M. Scavenging reactive oxygen species inhibits status epilepticus-induced neuroinflammation. Exp. Neurol., 2017, 298(Pt A), 13-22. doi: 10.1016/j.expneurol.2017.08.009
  9. Olowe, R.; Sandouka, S.; Saadi, A.; Shekh-Ahmad, T. Approaches for reactive oxygen species and oxidative stress quantification in epilepsy. Antioxidants, 2020, 9(10), 990. doi: 10.3390/antiox9100990 PMID: 33066477
  10. Parsons, A.L.M.; Bucknor, E.M.V.; Castroflorio, E.; Soares, T.R.; Oliver, P.L.; Rial, D. The interconnected mechanisms of oxidative stress and neuroinflammation in epilepsy. Antioxidants, 2022, 11(1), 157. doi: 10.3390/antiox11010157 PMID: 35052661
  11. Freitas, R.M. Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. Neurosci. Lett., 2009, 462(3), 225-229. doi: 10.1016/j.neulet.2009.07.037 PMID: 19616071
  12. Chen, S.; Chen, Y.; Zhang, Y.; Kuang, X.; Liu, Y.; Guo, M.; Ma, L.; Zhang, D.; Li, Q. Iron metabolism and ferroptosis in epilepsy. Front. Neurosci., 2020, 14, 601193. doi: 10.3389/fnins.2020.601193 PMID: 33424539
  13. Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; Morrison, B., III; Stockwell, B.R. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5), 1060-1072. doi: 10.1016/j.cell.2012.03.042 PMID: 22632970
  14. Cai, Y.; Yang, Z. Ferroptosis and its role in epilepsy. Front. Cell. Neurosci., 2021, 15, 696889. doi: 10.3389/fncel.2021.696889 PMID: 34335189
  15. Stockwell, B.R.; Friedmann Angeli, J.P.; Bayir, H.; Bush, A.I.; Conrad, M.; Dixon, S.J.; Fulda, S.; Gascón, S.; Hatzios, S.K.; Kagan, V.E.; Noel, K.; Jiang, X.; Linkermann, A.; Murphy, M.E.; Overholtzer, M.; Oyagi, A.; Pagnussat, G.C.; Park, J.; Ran, Q.; Rosenfeld, C.S.; Salnikow, K.; Tang, D.; Torti, F.M.; Torti, S.V.; Toyokuni, S.; Woerpel, K.A.; Zhang, D.D. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 2017, 171(2), 273-285. doi: 10.1016/j.cell.2017.09.021 PMID: 28985560
  16. Galluzzi, L.; Vitale, I.; Aaronson, S.A.; Abrams, J.M.; Adam, D.; Agostinis, P.; Alnemri, E.S.; Altucci, L.; Amelio, I.; Andrews, D.W.; Annicchiarico-Petruzzelli, M.; Antonov, A.V.; Arama, E.; Baehrecke, E.H.; Barlev, N.A.; Bazan, N.G.; Bernassola, F.; Bertrand, M.J.M.; Bianchi, K.; Blagosklonny, M.V.; Blomgren, K.; Borner, C.; Boya, P.; Brenner, C.; Campanella, M.; Candi, E.; Carmona-Gutierrez, D.; Cecconi, F.; Chan, F.K.M.; Chandel, N.S.; Cheng, E.H.; Chipuk, J.E.; Cidlowski, J.A.; Ciechanover, A.; Cohen, G.M.; Conrad, M.; Cubillos-Ruiz, J.R.; Czabotar, P.E.; D’Angiolella, V.; Dawson, T.M.; Dawson, V.L.; De Laurenzi, V.; De Maria, R.; Debatin, K.M.; DeBerardinis, R.J.; Deshmukh, M.; Di Daniele, N.; Di Virgilio, F.; Dixit, V.M.; Dixon, S.J.; Duckett, C.S.; Dynlacht, B.D.; El-Deiry, W.S.; Elrod, J.W.; Fimia, G.M.; Fulda, S.; García-Sáez, A.J.; Garg, A.D.; Garrido, C.; Gavathiotis, E.; Golstein, P.; Gottlieb, E.; Green, D.R.; Greene, L.A.; Gronemeyer, H.; Gross, A.; Hajnoczky, G.; Hardwick, J.M.; Harris, I.S.; Hengartner, M.O.; Hetz, C.; Ichijo, H.; Jäättelä, M.; Joseph, B.; Jost, P.J.; Juin, P.P.; Kaiser, W.J.; Karin, M.; Kaufmann, T.; Kepp, O.; Kimchi, A.; Kitsis, R.N.; Klionsky, D.J.; Knight, R.A.; Kumar, S.; Lee, S.W.; Lemasters, J.J.; Levine, B.; Linkermann, A.; Lipton, S.A.; Lockshin, R.A.; López-Otín, C.; Lowe, S.W.; Luedde, T.; Lugli, E.; MacFarlane, M.; Madeo, F.; Malewicz, M.; Malorni, W.; Manic, G.; Marine, J.C.; Martin, S.J.; Martinou, J.C.; Medema, J.P.; Mehlen, P.; Meier, P.; Melino, S.; Miao, E.A.; Molkentin, J.D.; Moll, U.M.; Muñoz-Pinedo, C.; Nagata, S.; Nuñez, G.; Oberst, A.; Oren, M.; Overholtzer, M.; Pagano, M.; Panaretakis, T.; Pasparakis, M.; Penninger, J.M.; Pereira, D.M.; Pervaiz, S.; Peter, M.E.; Piacentini, M.; Pinton, P.; Prehn, J.H.M.; Puthalakath, H.; Rabinovich, G.A.; Rehm, M.; Rizzuto, R.; Rodrigues, C.M.P.; Rubinsztein, D.C.; Rudel, T.; Ryan, K.M.; Sayan, E.; Scorrano, L.; Shao, F.; Shi, Y.; Silke, J.; Simon, H.U.; Sistigu, A.; Stockwell, B.R.; Strasser, A.; Szabadkai, G.; Tait, S.W.G.; Tang, D.; Tavernarakis, N.; Thorburn, A.; Tsujimoto, Y.; Turk, B.; Vanden Berghe, T.; Vandenabeele, P.; Vander Heiden, M.G.; Villunger, A.; Virgin, H.W.; Vousden, K.H.; Vucic, D.; Wagner, E.F.; Walczak, H.; Wallach, D.; Wang, Y.; Wells, J.A.; Wood, W.; Yuan, J.; Zakeri, Z.; Zhivotovsky, B.; Zitvogel, L.; Melino, G.; Kroemer, G. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ., 2018, 25(3), 486-541. doi: 10.1038/s41418-017-0012-4 PMID: 29362479
  17. Yang, W.S.; Kim, K.J.; Gaschler, M.M.; Patel, M.; Shchepinov, M.S.; Stockwell, B.R. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc. Natl. Acad. Sci. USA, 2016, 113(34), E4966-E4975. doi: 10.1073/pnas.1603244113 PMID: 27506793
  18. Chen, X.; Li, W.; Ren, J.; Huang, D.; He, W.; Song, Y.; Yang, C.; Li, W.; Zheng, X.; Chen, P.; Han, J. Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res., 2014, 24(1), 105-121. doi: 10.1038/cr.2013.171 PMID: 24366341
  19. Matsuda, T.; Zhai, P.; Sciarretta, S.; Zhang, Y.; Jeong, J.I.; Ikeda, S.; Park, J.; Hsu, C.P.; Tian, B.; Pan, D.; Sadoshima, J.; Del Re, D.P. NF2 activates hippo signaling and promotes ischemia/reperfusion injury in the heart. Circ. Res., 2016, 119(5), 596-606. doi: 10.1161/CIRCRESAHA.116.308586 PMID: 27402866
  20. Ursini, F.; Maiorino, M.; Valente, M.; Ferri, L.; Gregolin, C. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim. Biophys. Acta Lipids Lipid Metab., 1982, 710(2), 197-211. doi: 10.1016/0005-2760(82)90150-3 PMID: 7066358
  21. Mori, A.; Hiramatsu, M.; Yokoi, I.; Edamatsu, R. Biochemical pathogenesis of post-traumatic epilepsy. Pavlov. J. Biol. Sci., 1990, 25(2), 54-62. doi: 10.1007/BF02964604 PMID: 2122401
  22. Gianazza, E.; Brioschi, M.; Fernandez, A.M.; Banfi, C. Lipoxidation in cardiovascular diseases. Redox Biol., 2019, 23, 101119. doi: 10.1016/j.redox.2019.101119 PMID: 30833142
  23. Farzipour, S.; Shaghaghi, Z.; Motieian, S.; Alvandi, M.; Yazdi, A.; Asadzadeh, B.; Abbasi, S. Ferroptosis inhibitors as potential new therapeutic targets for cardiovascular disease. Mini Rev. Med. Chem., 2022, 22(17), 2271-2286. doi: 10.2174/1389557522666220218123404 PMID: 35184711
  24. Akyuz, E.; Doganyigit, Z.; Eroglu, E.; Moscovicz, F.; Merelli, A.; Lazarowski, A.; Auzmendi, J. Myocardial iron overload in an experimental model of sudden unexpected death in epilepsy. Front. Neurol., 2021, 12, 609236. doi: 10.3389/fneur.2021.609236 PMID: 33643194
  25. Pang, T.D.; Nearing, B.D.; Krishnamurthy, K.B.; Olin, B.; Schachter, S.C.; Verrier, R.L. Cardiac electrical instability in newly diagnosed/chronic epilepsy tracked by holter and ECG patch. Neurology, 2019, 93(10), 450-458. doi: 10.1212/WNL.0000000000008077 PMID: 31477610
  26. Verrier, R.L.; Pang, T.D.; Nearing, B.D.; Schachter, S.C. The epileptic heart: Concept and clinical evidence. Epilepsy Behav., 2020, 105, 106946. doi: 10.1016/j.yebeh.2020.106946 PMID: 32109857
  27. Verrier, R.L.; Pang, T.D.; Nearing, B.D.; Schachter, S.C.; Prolonged, Q.T. Prolonged QT interval predicts all-cause mortality in epilepsy patients: Diagnostic and therapeutic implications. Heart Rhythm, 2022, 19(4), 585-587. doi: 10.1016/j.hrthm.2022.01.015 PMID: 35033664
  28. Gatto, E.M.; Zurrú, C.M.; González, M.A.; Prolonged, Q.T. Prolonged QT syndrome presenting as epilepsy. Neurology, 1996, 46(4), 1188. doi: 10.1212/WNL.46.4.1188 PMID: 8780130
  29. Tigaran, S.; Mølgaard, H.; McClelland, R.; Dam, M.; Jaffe, A.S. Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients. Neurology, 2003, 60(3), 492-495. doi: 10.1212/01.WNL.0000042090.13247.48 PMID: 12578934
  30. Auzmendi, J.; Salgueiro, J.; Canellas, C.; Zubillaga, M.; Men, P.; Alicia, R.; Merelli, A.; Buchholz, B.; Ricardo, G.; Ramos, A.J.; Lazarowski, A.L. Pilocarpine-induced status epilepticus (SE) induces functional and histological p-glycoprotein overexpression in cardiomyocytes, heart dysfunction and high ratio of sudden death in rats. Pharmaceuticals, 2018, 11(1), 21.
  31. Tang, D.; Kroemer, G. Ferroptosis. Curr. Biol., 2020, 30(21), R1292-R1297. doi: 10.1016/j.cub.2020.09.068 PMID: 33142092
  32. Auzmendi, J.; Buchholz, B.; Salguero, J.; Cañellas, C.; Kelly, J.; Men, P.; Zubillaga, M.; Rossi, A.; Merelli, A.; Gelpi, R.; Ramos, A.; Lazarowski, A. Pilocarpine-induced status epilepticus is associated with p-glycoprotein induction in cardiomyocytes, electrocardiographic changes, and sudden death. Pharmaceuticals (Basel), 2018, 11(1), 21. doi: 10.3390/ph11010021 PMID: 29462915
  33. Auzmendi, J.; Puchulu, M.B.; Rodríguez, J.C.G.; Balaszczuk, A.M.; Lazarowski, A.; Merelli, A. EPO and EPO-receptor system as potential actionable mechanism for the protection of brain and heart in refractory epilepsy and SUDEP. Curr. Pharm. Des., 2020, 26(12), 1356-1364. doi: 10.2174/1381612826666200219095548 PMID: 32072891
  34. Auzmendi, J.; Lazarowski, A. Seizures induces hypoxia and hypoxia induces seizures: A perverse relationship that increases the risk of SUDEP. Neurol. Disord. Epilepsy J., 2020, 3(2), 135.
  35. Hentze, M.W.; Muckenthaler, M.U.; Galy, B.; Camaschella, C. Two to tango: Regulation of mammalian iron metabolism. Cell, 2010, 142(1), 24-38. doi: 10.1016/j.cell.2010.06.028 PMID: 20603012
  36. Fang, X.; Cai, Z.; Wang, H.; Han, D.; Cheng, Q.; Zhang, P.; Gao, F.; Yu, Y.; Song, Z.; Wu, Q.; An, P.; Huang, S.; Pan, J.; Chen, H.Z.; Chen, J.; Linkermann, A.; Min, J.; Wang, F. Loss of cardiac ferritin h facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ. Res., 2020, 127(4), 486-501. doi: 10.1161/CIRCRESAHA.120.316509 PMID: 32349646
  37. Stockwell, B.R. A powerful cell-protection system prevents cell death by ferroptosis. Nature, 2019, 575(7784), 597-598. doi: 10.1038/d41586-019-03145-8 PMID: 31768036
  38. Wagner, C.A.; Lang, F.; Bröer, S. Function and structure of heterodimeric amino acid transporters. Am. J. Physiol. Cell Physiol., 2001, 281(4), C1077-C1093. doi: 10.1152/ajpcell.2001.281.4.C1077 PMID: 11546643
  39. Xie, Y.; Hou, W.; Song, X.; Yu, Y.; Huang, J.; Sun, X.; Kang, R.; Tang, D. Ferroptosis: Process and function. Cell Death Differ., 2016, 23(3), 369-379. doi: 10.1038/cdd.2015.158 PMID: 26794443
  40. Hai, T.; Hartman, M.G. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: Activating transcription factor proteins and homeostasis. Gene, 2001, 273(1), 1-11. doi: 10.1016/S0378-1119(01)00551-0 PMID: 11483355
  41. Tang, Y.; Pacary, E.; Fréret, T.; Divoux, D.; Petit, E.; Schumann-Bard, P.; Bernaudin, M. Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: Identification of potential neuroprotective candidates for stroke. Neurobiol. Dis., 2006, 21(1), 18-28. doi: 10.1016/j.nbd.2005.06.002 PMID: 16040250
  42. Wang, L.; Liu, Y.; Du, T.; Yang, H.; Lei, L.; Guo, M.; Ding, H.F.; Zhang, J.; Wang, H.; Chen, X.; Yan, C. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc–. Cell Death Differ., 2020, 27(2), 662-675. doi: 10.1038/s41418-019-0380-z PMID: 31273299
  43. Wu, X.; Li, Y.; Zhang, S.; Zhou, X. Ferroptosis as a novel therapeutic target for cardiovascular disease. Theranostics, 2021, 11(7), 3052-3059. doi: 10.7150/thno.54113 PMID: 33537073
  44. Ursini, F.; Maiorino, M. Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic. Biol. Med., 2020, 152, 175-185. doi: 10.1016/j.freeradbiomed.2020.02.027 PMID: 32165281
  45. Baluchnejadmojarad, T.; Roghani, M. Coenzyme q10 ameliorates neurodegeneration, mossy fiber sprouting, and oxidative stress in intrahippocampal kainate model of temporal lobe epilepsy in rat. J. Mol. Neurosci., 2013, 49(1), 194-201. doi: 10.1007/s12031-012-9886-2 PMID: 23008120
  46. Zou, X.; Jiang, S.; Wu, Z.; Shi, Y.; Cai, S.; Zhu, R.; Chen, L. Effectiveness of deferoxamine on ferric chloride-induced epilepsy in rats. Brain Res., 2017, 1658, 25-30. doi: 10.1016/j.brainres.2017.01.001 PMID: 28063856
  47. Ye, Q.; Zeng, C.; Luo, C.; Wu, Y. Ferrostatin-1 mitigates cognitive impairment of epileptic rats by inhibiting P38 MAPK activation. Epilepsy Behav., 2020, 103(Pt A), 106670. doi: 10.1016/j.yebeh.2019.106670
  48. Aisen, P.; Enns, C.; Wessling-Resnick, M. Chemistry and biology of eukaryotic iron metabolism. Int. J. Biochem. Cell Biol., 2001, 33(10), 940-959. doi: 10.1016/S1357-2725(01)00063-2 PMID: 11470229
  49. Lieu, P.T.; Heiskala, M.; Peterson, P.A.; Yang, Y. The roles of iron in health and disease. Mol. Aspects Med., 2001, 22(1-2), 1-87. doi: 10.1016/S0098-2997(00)00006-6 PMID: 11207374
  50. Gulec, S.; Anderson, G.J.; Collins, J.F. Mechanistic and regulatory aspects of intestinal iron absorption. Am. J. Physiol. Gastrointest. Liver Physiol., 2014, 307(4), G397-G409. doi: 10.1152/ajpgi.00348.2013 PMID: 24994858
  51. Li, J.; Cao, F.; Yin, H.; Huang, Z.; Lin, Z.; Mao, N.; Sun, B.; Wang, G. Ferroptosis: past, present and future. Cell Death Dis., 2020, 11(2), 88. doi: 10.1038/s41419-020-2298-2 PMID: 32015325
  52. San Martin, C.D.; Garri, C.; Pizarro, F.; Walter, T.; Theil, E.C.; Núñez, M.T. Caco-2 intestinal epithelial cells absorb soybean ferritin by mu2 (AP2)-dependent endocytosis. J. Nutr., 2008, 138(4), 659-666. doi: 10.1093/jn/138.4.659 PMID: 18356317
  53. Morgan, E.H.; Oates, P.S. Mechanisms and regulation of intestinal iron absorption. Blood Cells Mol. Dis., 2002, 29(3), 384-399. doi: 10.1006/bcmd.2002.0578 PMID: 12547229
  54. Courville, P.; Chaloupka, R.; Cellier, M.F.M. Recent progress in structure–function analyses of Nramp proton-dependent metal-ion transporters membrane proteins in health and disease. Biochem. Cell Biol., 2006, 84(6), 960-978. doi: 10.1139/o06-193 PMID: 17215883
  55. Shawki, A.; Engevik, M.A.; Kim, R.S.; Knight, P.B.; Baik, R.A.; Anthony, S.R.; Worrell, R.T.; Shull, G.E.; Mackenzie, B. Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse. Am. J. Physiol. Gastrointest. Liver Physiol., 2016, 311(3), G423-G430. doi: 10.1152/ajpgi.00167.2016 PMID: 27390324
  56. McKie, A.T.; Barrow, D.; Latunde-Dada, G.O.; Rolfs, A.; Sager, G.; Mudaly, E.; Mudaly, M.; Richardson, C.; Barlow, D.; Bomford, A.; Peters, T.J.; Raja, K.B.; Shirali, S.; Hediger, M.A.; Farzaneh, F.; Simpson, R.J. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science, 2001, 291(5509), 1755-1759. doi: 10.1126/science.1057206 PMID: 11230685
  57. Schlottmann, F.; Vera-Aviles, M.; Latunde-Dada, G.O. Duodenal cytochrome b (Cybrd1) ferric reductase functional studies in cells. Metallomics, 2017, 9(10), 1389-1393. doi: 10.1039/C7MT00254H PMID: 28937159
  58. Chiabrando, D.; Vinchi, F.; Fiorito, V.; Mercurio, S.; Tolosano, E. Heme in pathophysiology: A matter of scavenging, metabolism and trafficking across cell membranes. Front. Pharmacol., 2014, 5, 61. doi: 10.3389/fphar.2014.00061 PMID: 24782769
  59. Parmley, R.T.; Barton, J.C.; Conrad, M.E.; Austin, R.L.; Holland, R.M. Ultrastructural cytochemistry and radioautography of hemoglobin-iron absorption. Exp. Mol. Pathol., 1981, 34(2), 131-144. doi: 10.1016/0014-4800(81)90070-8 PMID: 7202683
  60. Le Blanc, S.; Garrick, M.D.; Arredondo, M. Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism. Am. J. Physiol. Cell Physiol., 2012, 302(12), C1780-C1785. doi: 10.1152/ajpcell.00080.2012 PMID: 22496243
  61. Shayeghi, M.; Latunde-Dada, G.O.; Oakhill, J.S.; Laftah, A.H.; Takeuchi, K.; Halliday, N.; Khan, Y.; Warley, A.; McCann, F.E.; Hider, R.C.; Frazer, D.M.; Anderson, G.J.; Vulpe, C.D.; Simpson, R.J.; McKie, A.T. Identification of an intestinal heme transporter. Cell, 2005, 122(5), 789-801. doi: 10.1016/j.cell.2005.06.025 PMID: 16143108
  62. Hooda, J.; Shah, A.; Zhang, L. Heme, an essential nutrient from dietary proteins, critically impacts diverse physiological and pathological processes. Nutrients, 2014, 6(3), 1080-1102. doi: 10.3390/nu6031080 PMID: 24633395
  63. Yang, X.; Chen-Barrett, Y.; Arosio, P.; Chasteen, N.D. Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant human ferritins. Biochemistry, 1998, 37(27), 9743-9750. doi: 10.1021/bi973128a PMID: 9657687
  64. Liu, X.B.; Yang, F.; Haile, D.J. Functional consequences of ferroportin 1 mutations. Blood Cells Mol. Dis., 2005, 35(1), 33-46. doi: 10.1016/j.bcmd.2005.04.005 PMID: 15935710
  65. Qiu, A.; Jansen, M.; Sakaris, A.; Min, S.H.; Chattopadhyay, S.; Tsai, E.; Sandoval, C.; Zhao, R.; Akabas, M.H.; Goldman, I.D. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell, 2006, 127(5), 917-928. doi: 10.1016/j.cell.2006.09.041 PMID: 17129779
  66. Vulpe, C.D.; Kuo, Y.M.; Murphy, T.L.; Cowley, L.; Askwith, C.; Libina, N.; Gitschier, J.; Anderson, G.J. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the SLA mouse. Nat. Genet., 1999, 21(2), 195-199. doi: 10.1038/5979 PMID: 9988272
  67. Daher, R.; Manceau, H.; Karim, Z. Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease. Presse Med., 2017, 46(12), e272-e278. doi: 10.1016/j.lpm.2017.10.006 PMID: 29129410
  68. Yeh, K.; Yeh, M.; Mims, L.; Glass, J. Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(1), G55-G65. doi: 10.1152/ajpgi.90298.2008 PMID: 18974313
  69. Knutson, M.D. Iron-sensing proteins that regulate hepcidin and enteric iron absorption. Annu. Rev. Nutr., 2010, 30(1), 149-171. doi: 10.1146/annurev.nutr.012809.104801 PMID: 20415583
  70. Kawabata, H. Transferrin and transferrin receptors update. Free Radic. Biol. Med., 2019, 133, 46-54. doi: 10.1016/j.freeradbiomed.2018.06.037 PMID: 29969719
  71. Gammella, E.; Buratti, P.; Cairo, G.; Recalcati, S. The transferrin receptor: The cellular iron gate. Metallomics, 2017, 9(10), 1367-1375. doi: 10.1039/C7MT00143F PMID: 28671201
  72. El Hout, M.; Dos Santos, L.; Hamaï, A.; Mehrpour, M. A promising new approach to cancer therapy: Targeting iron metabolism in cancer stem cells. Semin. Cancer Biol., 2018, 53, 125-138. doi: 10.1016/j.semcancer.2018.07.009 PMID: 30071257
  73. Feng, H.; Schorpp, K.; Jin, J.; Yozwiak, C.E.; Hoffstrom, B.G.; Decker, A.M.; Rajbhandari, P.; Stokes, M.E.; Bender, H.G.; Csuka, J.M.; Upadhyayula, P.S.; Canoll, P.; Uchida, K.; Soni, R.K.; Hadian, K.; Stockwell, B.R. Transferrin receptor is a specific ferroptosis marker. Cell Rep., 2020, 30(10), 3411-3423.e7. doi: 10.1016/j.celrep.2020.02.049 PMID: 32160546
  74. Yan, H.; Zou, T.; Tuo, Q.; Xu, S.; Li, H.; Belaidi, A.A.; Lei, P. Ferroptosis: Mechanisms and links with diseases. Signal Transduct. Target. Ther., 2021, 6(1), 49. doi: 10.1038/s41392-020-00428-9 PMID: 33536413
  75. Gao, M.; Monian, P.; Quadri, N.; Ramasamy, R.; Jiang, X. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell, 2015, 59(2), 298-308. doi: 10.1016/j.molcel.2015.06.011 PMID: 26166707
  76. Sun, X.; Ou, Z.; Xie, M.; Kang, R.; Fan, Y.; Niu, X.; Wang, H.; Cao, L.; Tang, D. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene, 2015, 34(45), 5617-5625. doi: 10.1038/onc.2015.32 PMID: 25728673
  77. Wang, Z.; Ding, Y.; Wang, X.; Lu, S.; Wang, C.; He, C.; Wang, L.; Piao, M.; Chi, G.; Luo, Y.; Ge, P. Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT. Cancer Lett., 2018, 428, 21-33. doi: 10.1016/j.canlet.2018.04.021 PMID: 29702192
  78. Gao, G.; Li, J.; Zhang, Y.; Chang, Y.Z. Cellular iron metabolism and regulation. Adv. Exp. Med. Biol., 2019, 1173, 21-32. doi: 10.1007/978-981-13-9589-5_2 PMID: 31456203
  79. Fuhrmann, D.C.; Mondorf, A.; Beifuß, J.; Jung, M.; Brüne, B. Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol., 2020, 36, 101670. doi: 10.1016/j.redox.2020.101670 PMID: 32810738
  80. Kim, S.E.; Zhang, L.; Ma, K.; Riegman, M.; Chen, F.; Ingold, I.; Conrad, M.; Turker, M.Z.; Gao, M.; Jiang, X.; Monette, S.; Pauliah, M.; Gonen, M.; Zanzonico, P.; Quinn, T.; Wiesner, U.; Bradbury, M.S.; Overholtzer, M. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol., 2016, 11(11), 977-985. doi: 10.1038/nnano.2016.164 PMID: 27668796
  81. Basuli, D.; Tesfay, L.; Deng, Z.; Paul, B.; Yamamoto, Y.; Ning, G.; Xian, W.; McKeon, F.; Lynch, M.; Crum, C.P.; Hegde, P.; Brewer, M.; Wang, X.; Miller, L.D.; Dyment, N.; Torti, F.M.; Torti, S.V. Iron addiction: A novel therapeutic target in ovarian cancer. Oncogene, 2017, 36(29), 4089-4099. doi: 10.1038/onc.2017.11 PMID: 28319068
  82. Adedoyin, O.; Boddu, R.; Traylor, A.; Lever, J.M.; Bolisetty, S.; George, J.F.; Agarwal, A. Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells. Am. J. Physiol. Renal Physiol., 2018, 314(5), F702-F714. doi: 10.1152/ajprenal.00044.2017 PMID: 28515173
  83. Doll, S.; Conrad, M. Iron and ferroptosis: A still ill-defined liaison. IUBMB Life, 2017, 69(6), 423-434. doi: 10.1002/iub.1616 PMID: 28276141
  84. Ferreira, C.A.; Ni, D.; Rosenkrans, Z.T.; Cai, W. Scavenging of reactive oxygen and nitrogen species with nanomaterials. Nano Res., 2018, 11(10), 4955-4984. doi: 10.1007/s12274-018-2092-y PMID: 30450165
  85. Dröge, W. Free radicals in the physiological control of cell function. Physiol. Rev., 2002, 82(1), 47-95. doi: 10.1152/physrev.00018.2001 PMID: 11773609
  86. Bystrom, L.M.; Guzman, M.L.; Rivella, S. Iron and reactive oxygen species: Friends or foes of cancer cells? Antioxid. Redox Signal., 2014, 20(12), 1917-1924. doi: 10.1089/ars.2012.5014 PMID: 23198911
  87. Nita, M.; Grzybowski, A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev., 2016, 2016, 3164734. doi: 10.1155/2016/3164734 PMID: 26881021
  88. Shahidi, F.; Zhong, Y. Novel antioxidants in food quality preservation and health promotion. Eur. J. Lipid Sci. Technol., 2010, 112(9), 930-940. doi: 10.1002/ejlt.201000044
  89. Amer, J.; Ghoti, H.; Rachmilewitz, E.; Koren, A.; Levin, C.; Fibach, E. Red blood cells, platelets and polymorphonuclear neutrophils of patients with sickle cell disease exhibit oxidative stress that can be ameliorated by antioxidants. Br. J. Haematol., 2006, 132(1), 108-113. doi: 10.1111/j.1365-2141.2005.05834.x PMID: 16371026
  90. Sakellariou, G.K.; Jackson, M.J.; Vasilaki, A. Redefining the major contributors to superoxide production in contracting skeletal muscle. The role of NAD(P)H oxidases. Free Radic. Res., 2014, 48(1), 12-29. doi: 10.3109/10715762.2013.830718 PMID: 23915064
  91. Guerriero, G.; Trocchia, S.; Abdel-Gawad, F.K.; Ciarcia, G. Roles of reactive oxygen species in the spermatogenesis regulation. Front. Endocrinol. (Lausanne), 2014, 5, 56. doi: 10.3389/fendo.2014.00056 PMID: 24795696
  92. Izyumov, D.S.; Domnina, L.V.; Nepryakhina, O.K.; Avetisyan, A.V.; Golyshev, S.A.; Ivanova, O.Y.; Korotetskaya, M.V.; Lyamzaev, K.G.; Pletjushkina, O.Y.; Popova, E.N.; Chernyak, B.V. Mitochondria as source of reactive oxygen species under oxidative stress. Study with novel mitochondria-targeted antioxidants - the "Skulachev-ion" derivatives. Biochemistry (Mosc.), 2010, 75(2), 123-129. doi: 10.1134/S000629791002001X PMID: 20367598
  93. Lassègue, B.; San Martín, A.; Griendling, K.K. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ. Res., 2012, 110(10), 1364-1390. doi: 10.1161/CIRCRESAHA.111.243972 PMID: 22581922
  94. D’Autréaux, B.; Toledano, M.B. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol., 2007, 8(10), 813-824. doi: 10.1038/nrm2256 PMID: 17848967
  95. Auten, R.L.; Davis, J.M. Oxygen toxicity and reactive oxygen species: The devil is in the details. Pediatr. Res., 2009, 66(2), 121-127. doi: 10.1203/PDR.0b013e3181a9eafb PMID: 19390491
  96. Wen, X.; Wu, J.; Wang, F.; Liu, B.; Huang, C.; Wei, Y. Deconvoluting the role of reactive oxygen species and autophagy in human diseases. Free Radic. Biol. Med., 2013, 65, 402-410. doi: 10.1016/j.freeradbiomed.2013.07.013 PMID: 23872397
  97. Yang, W.S.; Stockwell, B.R. Ferroptosis: Death by lipid peroxidation. Trends Cell Biol., 2016, 26(3), 165-176. doi: 10.1016/j.tcb.2015.10.014 PMID: 26653790
  98. Conrad, M.; Pratt, D.A. The chemical basis of ferroptosis. Nat. Chem. Biol., 2019, 15(12), 1137-1147. doi: 10.1038/s41589-019-0408-1 PMID: 31740834
  99. Wenzel, S.E.; Tyurina, Y.Y.; Zhao, J.; St Croix, C.M.; Dar, H.H.; Mao, G.; Tyurin, V.A.; Anthonymuthu, T.S.; Kapralov, A.A.; Amoscato, A.A.; Mikulska-Ruminska, K.; Shrivastava, I.H.; Kenny, E.M.; Yang, Q.; Rosenbaum, J.C.; Sparvero, L.J.; Emlet, D.R.; Wen, X.; Minami, Y.; Qu, F.; Watkins, S.C.; Holman, T.R.; VanDemark, A.P.; Kellum, J.A.; Bahar, I.; Bayır, H.; Kagan, V.E. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell, 2017, 171(3), 628-641.e26. doi: 10.1016/j.cell.2017.09.044 PMID: 29053969
  100. Yin, H.; Xu, L.; Porter, N.A. Free radical lipid peroxidation: Mechanisms and analysis. Chem. Rev., 2011, 111(10), 5944-5972. doi: 10.1021/cr200084z PMID: 21861450
  101. Lee, J.Y.; Kim, W.K.; Bae, K.H.; Lee, S.C.; Lee, E.W. Lipid metabolism and ferroptosis. Biology (Basel), 2021, 10(3), 184. doi: 10.3390/biology10030184 PMID: 33801564
  102. Kagan, V.E.; Mao, G.; Qu, F.; Angeli, J.P.F.; Doll, S.; Croix, C.S.; Dar, H.H.; Liu, B.; Tyurin, V.A.; Ritov, V.B.; Kapralov, A.A.; Amoscato, A.A.; Jiang, J.; Anthonymuthu, T.; Mohammadyani, D.; Yang, Q.; Proneth, B.; Klein-Seetharaman, J.; Watkins, S.; Bahar, I.; Greenberger, J.; Mallampalli, R.K.; Stockwell, B.R.; Tyurina, Y.Y.; Conrad, M.; Bayır, H. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol., 2017, 13(1), 81-90. doi: 10.1038/nchembio.2238 PMID: 27842066
  103. Panaroni, C.; Fulzele, K.; Soucy, R.; Siu, K.T.; Mukaihara, K.; Huang, C.; Chattopadhyay, S.; Raje, N. Arachidonic acid induces ferroptosis-mediated cell-death in multiple myeloma. Blood, 2018, 132(Suppl. 1), 4498-4498. doi: 10.1182/blood-2018-99-118482
  104. Dixon, S.J.; Winter, G.E.; Musavi, L.S.; Lee, E.D.; Snijder, B.; Rebsamen, M.; Superti-Furga, G.; Stockwell, B.R. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem. Biol., 2015, 10(7), 1604-1609. doi: 10.1021/acschembio.5b00245 PMID: 25965523
  105. Doll, S.; Proneth, B.; Tyurina, Y.Y.; 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, C.H.; Wurst, W.; Schick, J.A.; Kagan, V.E.; Angeli, J.P.F.; Conrad, M. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol., 2017, 13(1), 91-98. doi: 10.1038/nchembio.2239 PMID: 27842070
  106. Skouta, R.; Dixon, S.J.; Wang, J.; Dunn, D.E.; Orman, M.; Shimada, K.; Rosenberg, P.A.; Lo, D.C.; Weinberg, J.M.; Linkermann, A.; Stockwell, B.R. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J. Am. Chem. Soc., 2014, 136(12), 4551-4556. doi: 10.1021/ja411006a PMID: 24592866
  107. Friedmann Angeli, J.P.; Schneider, M.; Proneth, B.; Tyurina, Y.Y.; Tyurin, V.A.; Hammond, V.J.; Herbach, N.; Aichler, M.; Walch, A.; Eggenhofer, E.; Basavarajappa, D.; Rådmark, O.; Kobayashi, S.; Seibt, T.; Beck, H.; Neff, F.; Esposito, I.; Wanke, R.; Förster, H.; Yefremova, O.; Heinrichmeyer, M.; Bornkamm, G.W.; Geissler, E.K.; Thomas, S.B.; Stockwell, B.R.; O’Donnell, V.B.; Kagan, V.E.; Schick, J.A.; Conrad, M. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol., 2014, 16(12), 1180-1191. doi: 10.1038/ncb3064 PMID: 25402683
  108. Küch, E.M.; Vellaramkalayil, R.; Zhang, I.; Lehnen, D.; Brügger, B.; Stremmel, W.; Ehehalt, R.; Poppelreuther, M.; Füllekrug, J. Differentially localized acyl-CoA synthetase 4 isoenzymes mediate the metabolic channeling of fatty acids towards phosphatidylinositol. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2014, 1841(2), 227-239. doi: 10.1016/j.bbalip.2013.10.018 PMID: 24201376
  109. Lei, P.; Bai, T.; Sun, Y. Mechanisms of ferroptosis and relations with regulated cell death: A review. Front. Physiol., 2019, 10, 139. doi: 10.3389/fphys.2019.00139 PMID: 30863316
  110. Kuhn, H.; Saam, J.; Eibach, S.; Holzhütter, H.G.; Ivanov, I.; Walther, M. Structural biology of mammalian lipoxygenases: Enzymatic consequences of targeted alterations of the protein structure. Biochem. Biophys. Res. Commun., 2005, 338(1), 93-101. doi: 10.1016/j.bbrc.2005.08.238 PMID: 16168952
  111. Hishikawa, D.; Shindou, H.; Kobayashi, S.; Nakanishi, H.; Taguchi, R.; Shimizu, T. Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity. Proc. Natl. Acad. Sci. USA, 2008, 105(8), 2830-2835. doi: 10.1073/pnas.0712245105 PMID: 18287005
  112. Ayala, A.; Muñoz, M.F.; Argüelles, S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev., 2014, 2014, 360438. doi: 10.1155/2014/360438 PMID: 24999379
  113. Reis, A.; Spickett, C.M. Chemistry of phospholipid oxidation. Biochim. Biophys. Acta Biomembr., 2012, 1818(10), 2374-2387. doi: 10.1016/j.bbamem.2012.02.002 PMID: 22342938
  114. Chen, J.J.; Galluzzi, L. Fighting resilient cancers with iron. Trends Cell Biol., 2018, 28(2), 77-78. doi: 10.1016/j.tcb.2017.11.007 PMID: 29223642
  115. Xiao, Y.; Meierhofer, D. Glutathione metabolism in renal cell carcinoma progression and implications for therapies. Int. J. Mol. Sci., 2019, 20(15), 3672. doi: 10.3390/ijms20153672 PMID: 31357507
  116. Pizzorno, J. Glutathione. Interg. Med., 2014, 13(1), 8-12.
  117. Liang, C.; Zhang, X.; Yang, M.; Dong, X. Recent progress in ferroptosis inducers for cancer therapy. Adv. Mater., 2019, 31(51), 1904197. doi: 10.1002/adma.201904197 PMID: 31595562
  118. Zhang, L.; Wang, L.; Ning, F-B.; Wang, T.; Liang, Y-C.; Liu, Y-L. Erythropoietin reduces hippocampus injury in neonatal rats with hypoxic ischemic brain damage via targeting matrix metalloprotein-2. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(19), 4327-4333. PMID: 29077163
  119. Meister, A. Glutathione; Metabolism and function via the γ-glutamyl cycle. Life Sci., 1974, 15(2), 177-190. doi: 10.1016/0024-3205(74)90206-9 PMID: 4620960
  120. Meister, A. The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies. Ann. Intern. Med., 1974, 81(2), 247-253. doi: 10.7326/0003-4819-81-2-247 PMID: 4152527
  121. Stark, A.A.; Porat, N.; Volohonsky, G.; Komlosh, A.; Bluvshtein, E.; Tubi, C.; Steinberg, P. The role of γ-glutamyl transpeptidase in the biosynthesis of glutathione. Biofactors, 2003, 17(1-4), 139-149. doi: 10.1002/biof.5520170114 PMID: 12897436
  122. Bjørklund, G.; Tinkov, A.A.; Hosnedlová, B.; Kizek, R.; Ajsuvakova, O.P.; Chirumbolo, S.; Skalnaya, M.G.; Peana, M.; Dadar, M.; El-Ansary, A.; Qasem, H.; Adams, J.B.; Aaseth, J.; Skalny, A.V. The role of glutathione redox imbalance in autism spectrum disorder: A review. Free Radic. Biol. Med., 2020, 160, 149-162. doi: 10.1016/j.freeradbiomed.2020.07.017 PMID: 32745763
  123. Cozza, G.; Rossetto, M.; Bosello-Travain, V.; Maiorino, M.; Roveri, A.; Toppo, S.; Zaccarin, M.; Zennaro, L.; Ursini, F. Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center. Free Radic. Biol. Med., 2017, 112, 1-11. doi: 10.1016/j.freeradbiomed.2017.07.010 PMID: 28709976
  124. Lewerenz, J.; Hewett, S.J.; Huang, Y.; Lambros, M.; Gout, P.W.; Kalivas, P.W.; Massie, A.; Smolders, I.; Methner, A.; Pergande, M.; Smith, S.B.; Ganapathy, V.; Maher, P. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid. Redox Signal., 2013, 18(5), 522-555. doi: 10.1089/ars.2011.4391 PMID: 22667998
  125. Bannai, S.; Kitamura, E. Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. J. Biol. Chem., 1980, 255(6), 2372-2376. doi: 10.1016/S0021-9258(19)85901-X PMID: 7358676
  126. Gochenauer, G.E.; Robinson, M.B. Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent l-3Hglutamate transport and expression of both system xc− subunits. J. Neurochem., 2001, 78(2), 276-286. doi: 10.1046/j.1471-4159.2001.00385.x PMID: 11461963
  127. Patel, S.A.; Warren, B.A.; Rhoderick, J.F.; Bridges, R.J. Differentiation of substrate and non-substrate inhibitors of transport system xc−: an obligate exchanger of L-glutamate and L-cystine. Neuropharmacology, 2004, 46(2), 273-284. doi: 10.1016/j.neuropharm.2003.08.006 PMID: 14680765
  128. Liu, L.; Liu, R.; Liu, Y.; Li, G.; Chen, Q.; Liu, X.; Ma, S. Cystine-glutamate antiporter XCT as a therapeutic target for cancer. Cell Biochem. Funct., 2021, 39(2), 174-179. doi: 10.1002/cbf.3581 PMID: 32749001
  129. Yamaguchi, I.; Yoshimura, S.H.; Katoh, H. High cell density increases glioblastoma cell viability under glucose deprivation via degradation of the cystine/glutamate transporter xCT (SLC7A11). J. Biol. Chem., 2020, 295(20), 6936-6945. doi: 10.1074/jbc.RA119.012213 PMID: 32265299
  130. Magtanong, L.; Ko, P.J.; Dixon, S.J. Emerging roles for lipids in non-apoptotic cell death. Cell Death Differ., 2016, 23(7), 1099-1109. doi: 10.1038/cdd.2016.25 PMID: 26967968
  131. Dächert, J.; Schoeneberger, H.; Rohde, K.; Fulda, S. RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death. Oncotarget, 2016, 7(39), 63779-63792. doi: 10.18632/oncotarget.11687 PMID: 27588473
  132. Sui, X.; Zhang, R.; Liu, S.; Duan, T.; Zhai, L.; Zhang, M.; Han, X.; Xiang, Y.; Huang, X.; Lin, H.; Xie, T. RSL3 drives ferroptosis through GPX4 inactivation and ROS production in colorectal cancer. Front. Pharmacol., 2018, 9, 1371. doi: 10.3389/fphar.2018.01371 PMID: 30524291
  133. Leestma, J.E.; Walczak, T.; Hughes, J.R.; Kalelkar, M.B.; Teas, S.S. A prospective study on sudden unexpected death in epilepsy. Ann. Neurol., 1989, 26(2), 195-203. doi: 10.1002/ana.410260203 PMID: 2774506
  134. Falconer, B.; Rajs, J. Post-mortem findings of cardiac lesions in epileptics: A preliminary report. Forensic Sci., 1976, 8(1), 63-71. doi: 10.1016/0300-9432(76)90048-0 PMID: 824190
  135. Natelson, B.H.; Suarez, R.V.; Terrence, C.F.; Turizo, R. Patients with epilepsy who die suddenly have cardiac disease. Arch. Neurol., 1998, 55(6), 857-860. doi: 10.1001/archneur.55.6.857 PMID: 9626779
  136. Fineschi, V.; Silver, M.D.; Karch, S.B.; Parolini, M.; Turillazzi, E.; Pomara, C.; Baroldi, G. Myocardial disarray: An architectural disorganization linked with adrenergic stress? Int. J. Cardiol., 2005, 99(2), 277-282. doi: 10.1016/j.ijcard.2004.01.022 PMID: 15749187
  137. Zhuo, L.; Zhang, Y.; Zielke, H.R.; Levine, B.; Zhang, X.; Chang, L.; Fowler, D.; Li, L. Sudden unexpected death in epilepsy: Evaluation of forensic autopsy cases. Forensic Sci. Int., 2012, 223(1-3), 171-175. doi: 10.1016/j.forsciint.2012.08.024 PMID: 22999232
  138. Goldberger, J.J.; Cain, M.E.; Hohnloser, S.H.; Kadish, A.H.; Knight, B.P.; Lauer, M.S.; Maron, B.J.; Page, R.L.; Passman, R.S.; Siscovick, D.; Stevenson, W.G.; Zipes, D.P. American Heart Association/american college of cardiology foundation/heart rhythm society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the american heart association council on clinical cardiology committee on electrocardiography and arrhythmias and council on epidemiology and prevention. Heart Rhythm, 2008, 5(10), e1-e21. doi: 10.1016/j.hrthm.2008.05.031 PMID: 18929319
  139. Zack, M.; Luncheon, C. Adults with an epilepsy history, notably those 45–64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history. Epilepsy Behav., 2018, 86, 208-210. doi: 10.1016/j.yebeh.2018.05.021 PMID: 29908906
  140. Szabó, C.Á.; Akopian, M.; González, D.A.; Garza, M.A.; Carless, M.A. Cardiac biomarkers associated with epilepsy in a captive baboon pedigree. Epilepsia, 2019, 60(11), e110-e114. doi: 10.1111/epi.16359 PMID: 31592545
  141. Tu, E.; Bagnall, R.D.; Duflou, J.; Semsarian, C. Post- mortem review and genetic analysis of sudden unexpected death in epilepsy (SUDEP) cases. Brain Pathol., 2011, 21(2), 201-208. doi: 10.1111/j.1750-3639.2010.00438.x PMID: 20875080
  142. Friedman, D.; Kannan, K.; Faustin, A.; Shroff, S.; Thomas, C.; Heguy, A.; Serrano, J.; Snuderl, M.; Devinsky, O. Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP). NPJ Genom. Med., 2018, 3(1), 9. doi: 10.1038/s41525-018-0048-5 PMID: 29619247
  143. Bagnall, R.D.; Crompton, D.E.; Petrovski, S.; Lam, L.; Cutmore, C.; Garry, S.I.; Sadleir, L.G.; Dibbens, L.M.; Cairns, A.; Kivity, S.; Afawi, Z.; Regan, B.M.; Duflou, J.; Berkovic, S.F.; Scheffer, I.E.; Semsarian, C. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann. Neurol., 2016, 79(4), 522-534. doi: 10.1002/ana.24596 PMID: 26704558
  144. Tester, D.J.; Ackerman, M.J. Genetics of long QT syndrome. Methodist DeBakey Cardiovasc. J., 2014, 10(1), 29-33. doi: 10.14797/mdcj-10-1-29 PMID: 24932360
  145. Auzmendi, J.; Akyuz, E.; Lazarowski, A. The role of p-glycoprotein (p-gp) and inwardly rectifying potassium (kir) channels in sudden unexpected death in Epilepsy (SUDEP). Epilepsy Behav., 2021, 121(Pt B), 106590. doi: 10.1016/j.yebeh.2019.106590
  146. Akyüz, E.; Üner, A.K.; Köklü, B.; Arulsamy, A.; Shaikh, M.F. Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology. J. Neurosci. Res., 2021, 99(9), 2059-2073. doi: 10.1002/jnr.24861 PMID: 34109651
  147. Merelli, A.; Ramos, A.J.; Lazarowski, A.; Auzmendi, J. Convulsive stress mimics brain hypoxia and promotes the P-glycoprotein (P-gp) and erythropoietin receptor overexpression. Front. Neurosci., 2019, 13, 750. doi: 10.3389/fnins.2019.00750 PMID: 31379495
  148. Ersoy Dursun, F.; Açıksarı, G.; Özkök, S.; İncealtın, O. Evaluation of electrocardiography, echocardiography and cardiac T2* for cardiac complications in beta thalassemia major. Int. J. Cardiovasc. Imag., 2022, 38(3), 533-542. doi: 10.1007/s10554-021-02421-x PMID: 34623560
  149. Engle, M.A.; Erlandson, M.; Smith, C.H. Late cardiac complications of chronic, severe, refractory anemia with hemochromatosis. Circulation, 1964, 30(5), 698-705. doi: 10.1161/01.CIR.30.5.698 PMID: 14226168
  150. Cecchetti, G.; Binda, A.; Piperno, A.; Nador, F.; Fargion, S.; Fiorelli, G. Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: Polygraphic and echocardiographic evaluation. Eur. Heart J., 1991, 12(2), 224-230. doi: 10.1093/oxfordjournals.eurheartj.a059873 PMID: 2044557
  151. Tadokoro, T.; Ikeda, M.; Ide, T.; Deguchi, H.; Ikeda, S.; Okabe, K.; Ishikita, A.; Matsushima, S.; Koumura, T.; Yamada, K.; Imai, H.; Tsutsui, H. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight, 2020, 5(9), e132747. doi: 10.1172/jci.insight.132747 PMID: 32376803
  152. Fang, X.; Wang, H.; Han, D.; Xie, E.; Yang, X.; Wei, J.; Gu, S.; Gao, F.; Zhu, N.; Yin, X.; Cheng, Q.; Zhang, P.; Dai, W.; Chen, J.; Yang, F.; Yang, H.T.; Linkermann, A.; Gu, W.; Min, J.; Wang, F. Ferroptosis as a target for protection against cardiomyopathy. Proc. Natl. Acad. Sci. USA, 2019, 116(7), 2672-2680. doi: 10.1073/pnas.1821022116 PMID: 30692261
  153. Conrad, M.; Proneth, B. Broken hearts: Iron overload, ferroptosis and cardiomyopathy. Cell Res., 2019, 29(4), 263-264. doi: 10.1038/s41422-019-0150-y PMID: 30809018
  154. Bai, T.; Li, M.; Liu, Y.; Qiao, Z.; Wang, Z. Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell. Free Radic. Biol. Med., 2020, 160, 92-102. doi: 10.1016/j.freeradbiomed.2020.07.026 PMID: 32768568
  155. Selim, M.H.; Ratan, R.R. The role of iron neurotoxicity in ischemic stroke. Ageing Res. Rev., 2004, 3(3), 345-353. doi: 10.1016/j.arr.2004.04.001 PMID: 15231241
  156. Ishimaru, H.; Ishikawa, K.; Ohe, Y.; Takahashi, A.; Tatemoto, K.; Maruyama, Y. Activation of iron handling system within the gerbil hippocampus after cerebral ischemia. Brain Res., 1996, 726(1-2), 23-30.
  157. Pereira, A.; Brandao, P.; Auzmendi, J.; Lazarowski, A. Hemosiderin, a possible biomarker for sudep? Rev. Neurociencias, 2021, 29, 1-13.
  158. Liu, X.J.; Lv, Y.F.; Cui, W.Z.; Li, Y.; Liu, Y.; Xue, Y.T.; Dong, F. Icariin inhibits hypoxia/reoxygenation-induced ferroptosis of cardiomyocytes via regulation of the Nrf2/HO-1 signaling pathway. FEBS Open Bio, 2021, 11(11), 2966-2976. doi: 10.1002/2211-5463.13276 PMID: 34407320
  159. Pansani, A.P.; Ghazale, P.P.; dos Santos, E.G.; dos Santos Borges, K.; Gomes, K.P.; Lacerda, I.S.; Castro, C.H.; Mendes, E.P.; dos Santos, F.C.A.; Biancardi, M.F.; Nejm, M.B.; Dogini, D.B.; Rabelo, L.A.; Nunes-Souza, V.; Scorza, F.A.; Colugnati, D.B. The number and periodicity of seizures induce cardiac remodeling and changes in micro-RNA expression in rats submitted to electric amygdala kindling model of epilepsy. Epilepsy Behav., 2021, 116, 107784. doi: 10.1016/j.yebeh.2021.107784 PMID: 33548915
  160. Castoldi, M.; Muckenthaler, M.U. Regulation of iron homeostasis by microRNAs. Cell. Mol. Life Sci., 2012, 69(23), 3945-3952. doi: 10.1007/s00018-012-1031-4 PMID: 22678662
  161. Alsharafi, W.A.; Xiao, B.; Abuhamed, M.M.; Luo, Z. miRNAs: Biological and clinical determinants in epilepsy. Front. Mol. Neurosci., 2015, 8(OCT), 59. doi: 10.3389/fnmol.2015.00059 PMID: 26528124
  162. Linkermann, A.; Skouta, R.; Himmerkus, N.; Mulay, S.R.; Dewitz, C.; De Zen, F.; Prokai, A.; Zuchtriegel, G.; Krombach, F.; Welz, P.S.; Weinlich, R.; Vanden Berghe, T.; Vandenabeele, P.; Pasparakis, M.; Bleich, M.; Weinberg, J.M.; Reichel, C.A.; Bräsen, J.H.; Kunzendorf, U.; Anders, H.J.; Stockwell, B.R.; Green, D.R.; Krautwald, S. Synchronized renal tubular cell death involves ferroptosis. Proc. Natl. Acad. Sci. USA, 2014, 111(47), 16836-16841. doi: 10.1073/pnas.1415518111 PMID: 25385600
  163. Matsushita, M.; Freigang, S.; Schneider, C.; Conrad, M.; Bornkamm, G.W.; Kopf, M. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J. Exp. Med., 2015, 212(4), 555-568. doi: 10.1084/jem.20140857 PMID: 25824823
  164. Dixon, S.J.; Patel, D.N.; Welsch, M.; Skouta, R.; Lee, E.D.; Hayano, M.; Thomas, A.G.; Gleason, C.E.; Tatonetti, N.P.; Slusher, B.S.; Stockwell, B.R. Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife, 2014, 3(3), e02523. doi: 10.7554/eLife.02523 PMID: 24844246
  165. Jiang, L.; Kon, N.; Li, T.; Wang, S.J.; Su, T.; Hibshoosh, H.; Baer, R.; Gu, W. Ferroptosis as a p53-mediated activity during tumour suppression. Nature, 2015, 520(7545), 57-62. doi: 10.1038/nature14344 PMID: 25799988
  166. Prakash, C.; Mishra, M.; Kumar, P.; Kumar, V.; Sharma, D. Dehydroepiandrosterone alleviates oxidative stress and apoptosis in iron-induced epilepsy via activation of Nrf2/ARE signal pathway. Brain Res. Bull., 2019, 153, 181-190. doi: 10.1016/j.brainresbull.2019.08.019 PMID: 31472186
  167. Kose, T.; Vera-Aviles, M.; Sharp, P.A.; Latunde-Dada, G.O. Curcumin and (−)- epigallocatechin-3-gallate protect murine min6 pancreatic beta-cells against iron toxicity and erastin-induced ferroptosis. Pharmaceuticals, 2019, 12(1), 26. doi: 10.3390/ph12010026 PMID: 30736288
  168. Liu, K.; Chen, S.; Lu, R. Identification of important genes related to ferroptosis and hypoxia in acute myocardial infarction based on WGCNA. Bioengineered, 2021, 12(1), 7950-7963. doi: 10.1080/21655979.2021.1984004 PMID: 34565282

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers