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Review Articles

Recent advances in iron homeostasis and regulation - a focus on epigenetic regulation and stroke

ORCID Icon, , &
Pages 375-383 | Received 29 Oct 2020, Accepted 17 Dec 2020, Published online: 07 Jan 2021

References

  • Kanamori Y, Murakami M, Matsui T, et al. Hepcidin expression in liver cells: evaluation of mRNA levels and transcriptional regulation. Gene. 2014;546(1):50–55.
  • Ganz T. Hepcidin-a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol. 2005;18(2):171–182.
  • Kulaksiz H, Theilig F, Bachmann S, et al. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J Endocrinol. 2005;184(2):361–370.
  • Santos-Silva A, Ribeiro S, Reis F, et al. Hepcidin in chronic kidney disease anemia. Vitam Horm. 2019;110:243–264.
  • Rishi G, Wallace DF, Subramaniam VN. Hepcidin: regulation of the master iron regulator. Biosci Rep. 2015;35(3):e00192.
  • De Domenico I, Ward DM, Kaplan J. Hepcidin and ferroportin: the new players in iron metabolism. Semin Liver Dis. 2011;31(3):272–279.
  • Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr. 2006;26:323–342.
  • Fernandes A, Preza GC, Phung Y, et al. The molecular basis of hepcidin-resistant hereditary hemochromatosis. Blood. 2009;114(2):437–443.
  • Clark RJ, Tan CC, Preza GC, et al. Understanding the structure/activity relationships of the iron regulatory peptide hepcidin. Chem Biol. 2011;18(3):336–343.
  • Ganz T, Nemeth E. The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders. Hematology Am Soc Hematol Educ Program. 2011;2011:538–542.
  • Liu XB, Nguyen NB, Marquess KD, et al. Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages. Blood Cells Mol Dis. 2005;35(1):47–56.
  • Bekri S, Gual P, Anty R, et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology. 2006;131(3):788–796.
  • Rochette L, Gudjoncik A, Guenancia C, et al. The iron-regulatory hormone hepcidin: a possible therapeutic target? Pharmacol Ther. 2015;146:35–52.
  • Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276(11):7811–7819.
  • Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta. 2012;1823(9):1434–1443.
  • Sharp PA, Clarkson R, Hussain A, et al. DNA methylation of hepatic iron sensing genes and the regulation of hepcidin expression. PLoS One. 2018;13(5):e0197863.
  • Lopez P, Castro A, Florez M, et al. miR-155 and miR-122 expression of spermatozoa in obese subjects. Front Genet. 2018;9:175.
  • Wang SM, Fu LJ, Duan XL, et al. Role of hepcidin in murine brain iron metabolism. Cell Mol Life Sci. 2010;67(1):123–133.
  • Ding H, Yan CZ, Shi H, et al. Hepcidin is involved in iron regulation in the ischemic brain. PLoS One. 2011;6(9):e25324.
  • Tan G, Liu L, He Z, et al. Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats. Mol Cell Biochem. 2016;418(1–2):31–38.
  • Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–1072.
  • Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016;73(11–12):2195–2209.
  • Yan N, Zhang JJ. The emerging roles of ferroptosis in vascular cognitive impairment. Front Neurosci. 2019;13:811.
  • Bogdan AR, Miyazawa M, Hashimoto K, et al. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 2016;41(3):274–286.
  • Fanzani A, Poli M. Iron, oxidative damage and ferroptosis in rhabdomyosarcoma. Int J Mol Sci. 2017;18(8):1718.
  • Geng N, Shi BJ, Li SL, et al. Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells. Eur Rev Med Pharmacol Sci. 2018;22(12):3826–3836.
  • Yang WS, Sri Ramaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156(1–2):317–331.
  • Wang Y, Yang L, Zhang X, et al. Epigenetic regulation of ferroptosis by H2B monoubiquitination and p53. EMBO Rep. 2019;20(7):e47563.
  • Zhang Y, Shi J, Liu X, et al. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol. 2018;20(10):1181–1192.
  • Zhang X, Sui S, Wang L, et al. Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin. J Cell Physiol. 2020;235(4):3425–3437.
  • Lee P, Peng H, Gelbart T, et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA. 2005;102(6):1906–1910.
  • Stoian I, Manolescu B, Atanasiu V, et al. IL-6 - STAT-3 - hepcidin: linking inflammation to the iron metabolism. Rom J Intern Med. 2007;45(3):305–309.
  • Verga Falzacappa MV, Vujic Spasic M, Kessler R, et al. STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood. 2007;109(1):353–358.
  • Ruchala P, Nemeth E. The pathophysiology and pharmacology of hepcidin. Trends Pharmacol Sci. 2014;35(3):155–161.
  • Yin X, Wu Q, Monga J, et al. HDAC1 governs iron homeostasis independent of histone deacetylation in iron-overload murine models. Antioxid Redox Signal. 2018;28(13):1224–1237.
  • Pasricha SR, Lim PJ, Duarte TL, et al. Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nat Commun. 2017;8(1):403.
  • Vanhees K, Godschalk RW, Sanders A, et al. Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. Toxicology. 2011;290(2–3):350–358.
  • Udali S, Castagna A, Corbella M, et al. Hepcidin and DNA promoter methylation in hepatocellular carcinoma. Eur J Clin Invest. 2018;48(2):e12870.
  • Huang Y, Zhang H, Wang C, et al. DNA methylation suppresses liver Hamp expression in response to iron deficiency after bariatric surgery. Surg Obes Relat Dis. 2020;16(1):109–118.
  • Huang YH, Kuo HC, Li SC, et al. HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease. J Mol Cell Cardiol. 2018;117:82–87.
  • Kim K, Lee YS, Jeong S, et al. A small molecule, 4-phenylbutyric acid, suppresses HCV replication via epigenetically induced hepatic hepcidin. Int J Mol Sci. 2020;21(15):5516.
  • Chekhun VF, Lozovska YV, Naleskina LA, et al. Modifying effects of 5-azacytidine on metal-containing proteins profile in Guerin carcinoma with different sensitivity to cytostatics. Exp Oncol. 2016;38(4):283–287.
  • Tao Y, Wu Q, Guo X, et al. MBD5 regulates iron metabolism via methylation-independent genomic targeting of Fth1 through KAT2A in mice. Br J Haematol. 2014;166(2):279–291.
  • Zhao B, Yang Y, Wang X, et al. Redox-active quinones induces genome-wide DNA methylation changes by an iron-mediated and Tet-dependent mechanism. Nucleic Acids Res. 2014;42(3):1593–1605.
  • Guaraldo M, Santambrogio P, Rovelli E, et al. Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control. Sci Rep. 2016;6:33432.
  • da Silva VK, de Freitas BS, Dornelles VC, et al. Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: reversal by cannabidiol. Brain Res Bull. 2018;139:1–8.
  • Jiang B, Moskovitz J. The functions of the mammalian methionine sulfoxide reductase system and related diseases. Antioxidants (Basel) 2018;7(9):122.
  • Bulvik B, Grinberg L, Eliashar R, et al. Iron, ferritin and proteins of the methionine-centered redox cycle in young and old rat hearts. Mech Ageing Dev. 2009;130(3):139–144.
  • Grievink H, Zeltcer G, Drenger B, et al. Protection by nitric oxide donors of isolated rat hearts is associated with activation of redox metabolism and ferritin accumulation. PLoS One. 2016;11(7):e0159951.
  • Word TA, Larsen RW. Photoacoustic calorimetry studies of CO photo-dissociation from chloramine-T modified horse heart cytochrome-c. Arch Biochem Biophys. 2016;612:17–21.
  • Sideri TC, Willetts SA, Avery SV. Methionine sulphoxide reductases protect iron-sulphur clusters from oxidative inactivation in yeast. Microbiology (Reading). 2009;155(Pt 2):612–623.
  • Aluri HS, Simpson DC, Allegood JC, et al. Electron flow into cytochrome c coupled with reactive oxygen species from the electron transport chain converts cytochrome c to a cardiolipin peroxidase: role during ischemia-reperfusion. Biochim Biophys Acta. 2014;1840(11):3199–3207.
  • Kawai K, Li YS, Song MF, et al. DNA methylation by dimethyl sulfoxide and methionine sulfoxide triggered by hydroxyl radical and implications for epigenetic modifications. Bioorg Med Chem Lett. 2010;20(1):260–265.
  • Hanson LR, Roeytenberg A, Martinez PM, et al. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther. 2009;330(3):679–686.
  • Prass K, Ruscher K, Karsch M, et al. Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cereb Blood Flow Metab. 2002;22(5):520–525.
  • Hemorrhagic Stroke Academia Industry Roundtable Participants. Unmet needs and challenges in clinical research of intracerebral hemorrhage. Stroke. 2018;49(5):1299–1307.
  • Garton T, Keep RF, Hua Y, et al. Brain iron overload following intracranial haemorrhage. Stroke Vasc Neurol. 2016;1(4):172–184.
  • Almutairi MMA, Xu G, Shi H. Iron pathophysiology in stroke. Adv Exp Med Biol. 2019;1173:105–123.
  • Li L, Li YW, Zhao JY, et al. Quantitative analysis of iron concentration and expression of ferroportin 1 in the cortex and hippocampus of rats induced by cerebral ischemia. J Clin Neurosci. 2009;16(11):1466–1472.
  • Wang G, Hu W, Tang Q, et al. Effect comparison of both iron chelators on outcomes, iron deposit, and iron transporters after intracerebral hemorrhage in rats. Mol Neurobiol. 2016;53(6):3576–3585.
  • Vela D. Hepcidin, an emerging and important player in brain iron homeostasis. J Transl Med. 2018;16(1):25.
  • Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–285.
  • Chen L, Hambright WS, Na R, et al. Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis. J Biol Chem. 2015;290(47):28097–28106.
  • Hambright WS, Fonseca RS, Chen L, et al. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol. 2017;12:8–17.
  • Tuo QZ, Lei P, Jackman KA, et al. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol Psychiatry. 2017;22(11):1520–1530.
  • Guan X, Li X, Yang X, et al. The neuroprotective effects of carvacrol on ischemia/reperfusion-induced hippocampal neuronal impairment by ferroptosis mitigation. Life Sci. 2019;235:116795.
  • Li Q, Han X, Lan X, et al. Inhibition of neuronal ferroptosis protects hemorrhagic brain. JCI Insight. 2017;2(7):e90777.
  • Zhang Z, Wu Y, Yuan S, et al. Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage. Brain Res. 2018;1701:112–125.
  • Alim I, Caulfield JT, Chen Y, et al. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell. 2019;177(5):1262–1279.e25.
  • Chen B, Chen Z, Liu M, et al. Inhibition of neuronal ferroptosis in the acute phase of intracerebral hemorrhage shows long-term cerebroprotective effects. Brain Res Bull. 2019;153:122–132.
  • Xia Y, Sun X, Luo Y, et al. Ferroptosis contributes to isoflurane neurotoxicity. Front Mol Neurosci. 2018;11:486.
  • Kabiraj P, Valenzuela CA, Marin JE, et al. The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells. Protein J. 2015;34(5):349–358.
  • Karuppagounder SS, Alin L, Chen Y, 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. 2018;84(6):854–872.
  • Guo S, Jiang X, Wang Y, et al. The protective role of TET2 in erythroid iron homeostasis against oxidative stress and erythropoiesis. Cell Signal. 2017;38:106–115.
  • Rogers JT, Xia N, Wong A, et al. Targeting the iron-response elements of the mRNAs for the Alzheimer's amyloid precursor protein and ferritin to treat acute lead and manganese neurotoxicity. Int J Mol Sci. 2019;20(4):994.
  • Yu M, Zhou X, Ju L, et al. Characteristics of iron status, oxidation response, and DNA methylation profile in response to occupational iron oxide nanoparticles exposure. Toxicol Ind Health. 2020;36(3):170–180.
  • Helgudottir SS, Lichota J, Burkhart A, et al. Hepcidin mediates transcriptional changes in ferroportin mRNA in differentiated neuronal-like PC12 cells subjected to iron challenge. Mol Neurobiol. 2019;56(4):2362–2374.
  • Blanchette NL, Manz DH, Torti FM, et al. Modulation of hepcidin to treat iron deregulation: potential clinical applications. Expert Rev Hematol. 2016;9(2):169–186.
  • Chekhun VF, Lukianova NY, Borikun TV, et al. Artemisinin modulating effect on human breast cancer cell lines with different sensitivity to cytostatics. Exp Oncol. 2017;39(1):25–29.
  • Wu Y, Zhang S, Gong X, et al. The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression. Mol Cancer. 2020;19(1):39.

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