head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing Ltd.
ISSN: 1312-773X (Online)
Issue: 2019, vol. 25, issue1
Subject Area: Medicine
DOI: 10.5272/jimab.2019251.2414
Published online: 14 March 2019

Review article

J of IMAB. 2019 Jan-Mar;25(1):2414-2418
Yavor KashlovORCID logo Corresponding Autoremail, Maria DimovaORCID logo,
Department of Internal Medicine, UMHAT St. Marina, Faculty of Medicine, Medical University, Varna, Bulgaria.

Iron (Fe) is the fourth most common element in the earth's crust, and plays a significant role in the human body.It is important for cell survival due toits involvement in the transport of oxygen, in DNA biosynthesis, adenosine triphosphate (ATP) synthesis, as well as an auxiliary factor of various proteins in the tricarboxylic acid cycle (TCA). It has also been found that iron is closely related to the onset and progression of various cancers and disturbances in its metabolism can stimulate the growth of tumor cells. In addition, divalent iron significantly accelerates the lipid peroxidation of saturated fatty acids.

Keywords: Ferroptosis, adenosine triphosphate (ATP), erastin, cell death, apoptosis, necrosis,

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Please cite this article as: Kashlov Y, Dimova M. Ferroptosis and its potential role in Cardiovascular diseases. J of IMAB. 2019 Jan-Mar;25(1):2414-2418. DOI: 10.5272/jimab.2019251.2414

Corresponding AutorCorrespondence to: Yavor Kashlov, First Clinic of Cardiology, Department of Internal Medicine, Universiy Hospital St. Marina, Varna; 1, Hr. Smirnensky blvd., Varna, Bulgaria; E-mail: javork@abv.bg

1. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal.2012 May;24(5):981-90. [PubMed] [Crossref]
2.  Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. [PubMed] [Crossref]
3. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014 Jan; 156(1-2): 317-31. [PubMed] [Crossref]
4. Lachaier E, Louandre C, Godin C, Saidak Z, Baert M, Diouf M, et al. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res.2014 Nov;34(11): 6417-22. [PubMed]
5. Ooko E, Saeed ME, Kadioglu O, Sarvi S, Colak M, Elmasaoudi  K, et al. Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells. Phytomedicine. 2015 Oct; 22(11): 1045-54. [PubMed] [Crossref]
6. Yang WS, Stockwell BR. Ferroptosis: Death by Lipid Peroxidation. Trends Cell Biol.2016 Mar; 26(3): 165-76. [PubMed] [Crossref]
7. Eling N, Reuter L, Hazin J, Hamacher-Brady A, Brady NR. Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2015. May; 2(5): 517-32. [PubMed] [Crossref]
8. Louandre C, Marcq I, Bouhlal H, Lachaier E., Godin C, Saidak  Z, et al. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells. Cancer Lett. 2015 Jan; 356(2 Pt B): 971-7.[PubMed] [Corssref]
9. Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer cell. 2003 Mar; 3(3): 285-96. [PubMed]
10. Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008 Mar; 15(3): 234-45. [PubMed] [Crossref]
11. Louandre C, Ezzoukhry Z, Godin C, Barbare JC, Maziere JC, Chauffert B, et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib Int J Cancer. 2013 Oct; 133(7): 1732-42. [PubMed] [Crossref]
12. Abrams RP, Carroll WL, Woerpel KA. Five-Membered Ring Peroxide Selectively Initiates Ferroptosis in Cancer Cells. ACS Chem Biol.2016 May; 11(5): 1305-12. [PubMed] [Crossref]
13. Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016 Jun; 73(11-12): 2195-209. [PubMed] [Crossref]
14. Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, et al. Ferroptosis: process and function. Cell Death Differ. 2016  Mar; 23(3): 369-79. [PubMed] [Crossref]
15. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer.1972 Aug; 26(4): 239-57. [PubMed]
16. Schweichel JU, Merker HJ. The morphology of various types of cell death in prenatal tissues. Teratology. 1973 Jun; 7(3): 253-66. [PubMed] [Crossref]
17. Clarke PG. Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl).1990 Mar; 181(3): 195-213. [PubMed]
18. Yu H, Guo P, Xie X, Wang Y, Chen G. Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cel lMolMed. 2017 Apr; 21(4): 648-57. [PubMed] [Crossref]
19. Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R, Sasaki M, et al. An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem J.2016 Mar; 473(6): 769-77. [PubMed] [Crossref]
20. Sato H, Tamba M, Ishii T, Bannai S. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem. 1999 Apr; 274(17): 11455-8. [PubMed]
21. Bridges RJ, Natale NR, Patel SA. System xc(-) cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol. 2012 Jan; 165(1): 20-34. [PubMed] [Crossref]
22. Lo M, Wang YZ, Gout PW. The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases J Cell Physiol. 2008 Jun; 215(3): 593-602. [PubMed] [Crossref]
23. Tan S, Schubert D, Maher P. Oxytosis: A novel form of programmed cell death. Curr Top Med Chem. 2001 Dec; 1(6): 497-506. [PubMed
24. Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol.2014 Jan; 10(1): 9-17. [PubMed] [Crossref]
25. Bannai S, Kitamura E. Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. J Biol Chem.1980 Mar; 255(6): 2372-6. [PubMed]
26. Wolpaw AJ., Shimada K, Skouta R, Welsch ME, Akavia UD, Pe'er D, et al. Modulatory profiling identifies mechanisms of small molecule-induced cell death. Proc Natl Acad< Sci USA. 2011 Sep; 108(39): E771-80. [PubMed] [Crossref]
27. Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M, Shimada K, et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J Am Chem Soc.2014 Mar; 136(12): 4551-6. [PubMed] [Crossref]
28. Kremastinos DT, Farmakis D. Iron overload cardiomyopathy in clinical practice. Circulation. 2011 Nov; 124(20): 2253-63. [PubMed] [Crossref]
29. Miranda CJ, Makui H, Soares RJ, Bilodeau M, Mui J, Vali H, et al. Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin. Blood 2003. Oct; 102(7): 2574-80. [PubMed] [Crossref]
30. Nitenberg A, Ledoux S, Valensi P, Sachs R, Antony I. Coronary microvascular adaptation to myocardial metabolic demand can be restored by inhibition of iron-catalyzed formation of oxygen free radicals in type 2 diabetic patients. Diabetes 2002. Mar; 51(3): 813-8. [PubMed]
31. Lapenna D, Ciofani G, Pierdomenico SD, Giamberardino MA. Porreca E. Iron status and oxidative stress in the aged rabbit heart. J Mol Cell Cardiol. 2018 Jan; 114: 328-33. [PubMed] [Crossref]
32. Liu B, Zhao C, Li H, Chen X, Ding Y, Xu S. Puerarin protects against heart failure induced by pressure overload through mitigation of ferroptosis. Biochem Biophys Res Commun. 2018 Feb; 497(1): 233-40. [PubMed] [Crossref
33. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and Transferrin Regulate Ferroptosis. Mol Cell.2015 Jul; 59(2): 298-308. [PubMed] [Crossref]
34. Baba Y, Higa JK, Shimada BK, Horiuchi KM, Suhara T, Kobayashi M, et al. Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H659-H668. [PubMed] [Crossref]
35. Zhou YX, Zhang H, Peng C. Puerarin: a review of pharmacological effects. Phytother Res. 2014 Jul; 28(7): 961-75. [PubMed] [Crossref].

Received: 20 December 2018
Published online: 14 March 2019

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