СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О МЕТАБОЛИЗМЕ ЖЕЛЕЗА

В представленном обзоре литературы проведен анализ современных представлений о метаболизме железа. Одним из перспективных направлений исследования является детальное изучение сигнальных механизмов, ведущих к активации гепсидина, а также определение и изучение регуляторных взаимосвязей между системным и клеточным метаболизмом железа. Остаются до конца не изученными механизмы транспорта железа через мембраны внутриклеточных органелл. Исследования в этом направлении имеют не только биологическое, но медицинское значение. Так, ось гепсидин-ферропортин позиционируется как привлекательная мишень для разработки лекарств. Предполагается, что IRP1 и IRP2 участвуют не только в регуляции метаболизма железа, но и играют самостоятельную роль в механизмах развития рака.

1. Левина А. А. Гепсидин как регулятор гомеостаза железа /А. А. Левина, Т. В. Казюкова, Н. В. Цветаева //Педиатрия. - 2008. - V. 87 (1). - P. 67-74.

2. Маянский Н. А. Гепцидин: основной регулятор обмена железа и новый диагностический маркер /Н. А. Маянский, Е. Л. Семикина //Вопр. диагностики в педиатрии. -2009. - V. 1. - P. 18-23.

3. Anderson G. J. Iron absorption and metabolism /G. J. Anderson, D. M. Frazer, G. D. McLaren //Curr. Opin. Gastroenterol. - 2009. - V. 25 (2). - P. 129-135.

4. Arosio P. Ferritin, cellular iron storage and regulation /P. Arosio, L. Elia, M. Poli //UBMB Life. - 2017. - V. 69 (6). - P. 414-422.

5. Arosio P. Ferritins: a family of molecules for iron storage, antioxidation and more /P. Arosio, R. Ingrassia, P. Cavadini //Biochim. Biophys. Acta. - 2009. - V. 1790. - P. 589-599.

6. Babitt J. L. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression /J. L. Babitt, F. W. Huang, D. M. Wrighting //Nat. Genet. - 2006. - V. 38. - P. 531-539.

7. Bou-Abdallah F. Reductive Mobilization of Iron from Intact Ferritin: Mechanisms and Physiological Implication /F. Bou-Abdallah, J. J. Paliakkara, G. Melman //Pharmaceuticals (Basel). -2018. - V. 11 (4). - P. 120.

8. De Domenico I. Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome /I. De Domenico, M. B. Vaughn, L. Li //EMBO J. - 2006. - V. 25. - P. 5396-5404.

9. Finberg K. E. Regulation of systemic iron homeostasis //Curr. Opin. Hematol. - 2013. - V. 20 (3). - P. 208-214.

10. Galaris D. Oxidative stress and iron homeostasis: mechanistic and health aspects /D. Galaris, K. Pantopoulos //Crit. Rev. Clin. Lab. Sci. - 2008. - V. 45. - P. 1-23.

11. Gunshin H. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver /H. Gunshin, Y. Fujiwara, A. O. Custodio //J. Clin. Invest. - 2005. - V. 115. - P. 1258-1266.

12. Hentze M. W. Two to tango: regulation of mammalian iron metabolism /M. W. Hentze, M. U. Muckenthaler, B. Galy //Cell. - 2010. - V. 142. - P. 24-38.

13. Johnson D. C. Structure, function, and formation of biological iron-sulfur clusters /D. C. Johnson, D. R. Dean, A. D. Smith //Annu. Rev. Biochem. - 2005. - V. 74. - P. 247-281.

14. Kato J. Iron/IRP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1 and ferritin during human erythroid differentiation /J. Kato, M. Kobune, S. Ohkubo //Exp. Hematol. - 2007. - V. 35. - P. 879-887.

15. Keel S. B. A heme export protein is required for red blood cell differentiation and iron homeostasis /S. B. Keel, R. T. Doty, Z. Yang // Science. - 2008. - V. 319. - P. 825-828.

16. Kidane T. Z. Release of iron from ferritin requires lysosomal activity /T. Z. Kidane, E. Sauble, M. C. Linder //Am. J. Physiol. Cell Physiol. -2006. - V. 291. - C445-C455.

17. La A. Mobilization of iron from ferritin: New steps and details /A. La, T. Nguyen, K. Tran. - Metallomics. - 2018. - V. 10. - P. 154-168.

18. Lee P. L. Regulation of hepcidin and iron-overload disease /P. L. Lee, E. Beutler // Annu. Rev. Pathol. - 2009. - V. 4. - P. 489-515.

19. Lill R. Function and biogenesis of iron-sulphur proteins //Nature. - 2009. - V. 460. - P. 831-838.

20. Linder M. C. Mobilization of Stored Iron in Mammals: A Review //Nutrients. - 2013. - V. 5 (10). - P. 4022-4050.

21. Ma J. Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation /J. Ma, S. Haldar, M. A. Khan //Proc. Natl. Acad. Sci. U S A. - 2011. - V. 109. - P. 8417-8422.

22. Nemeth E. The role of hepcidin in iron metabolism /E. Nemeth, T. Ganz //Acta Haematol. - 2009. - V. 122. - P. 78-86.

23. Ohgami R. S. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells /R. S. Ohgami, D. R. Campagna, E. L. Greer //Nat. Genet. - 2005. - V. 37. - P. 1264-1269.

24. Olsson K. S. Comment to: Hepcidin: from discovery to differential diagnosis /K. S. Olsson, A. Norrby //Haematologica. - 2008. - V. 93. - P. 90-97.

25. Pak M. Suppression of hepcidin during anemia requires erythropoietic activity /M. Pak, M. A. Lopez, V. Gabayan //Blood. - 2006. - V. 108. - P. 3730-3735.

26. Pantopoulos K. Iron metabolism and the IRE/IRP regulatory system: an update //Ann. NY Acad. Sci. - 2004. - V. 1012. - P. 1-13.

27. Paradkar P. N. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2 /P. N. Paradkar, K. B. Zumbrennen, B. H. Paw //Mol. Cell. Biol. -2009. - V. 29. - P. 1007-1016.

28. Piccinelli P. Evolution of the iron-responsive element /P. Piccinelli, T. Samuelsson //RNA. - 2007. - V. 13. - P. 952-966.

29. Ponka P. Function and regulation of transferrin and ferritin /P. Ponka, C. Beaumont, D. R. Richardson //Semin. Hematol. - 1998. - V. 35. - P. 35-54.

30. Recalcati S. Molecular regulation of cellular iron balance //S. Recalcati, E. Gammella, P. Buratti //IUBMB Life. - 2017. - V. 69 (6). - P. 389-398.

31. Richardson D. R. Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol /D. R. Richardson, D. J. Lane, E. M. Becker //Proc. Natl. Acad. Sci. U.S.A. - 2010. - V. 107. - P. 1077510782.

32. Ryter S. W. The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro and antioxidant properties /S. W. Ryter, R. M. Tyrrell //Free Radical. Biol. Med. - 2000. - V. 28. - P. 289-309.

33. Schmidt P. J. Regulation of Iron Metabolism by Hepcidin under Conditions of Inflammation //J. Biol. Chem. - 2015. - V. 290 (31). - P. 18975-18983.

34. Shaw G. C. Mitoferrin is essential for erythroid iron assimilation /G. C. Shaw, J. J. Cope, L. Li. - Nature. - 2006. - V. 440. - P. 96100.

35. Shi H. A cytosolic iron chaperone that delivers iron to ferritin /H. Shi, K. Z. Bencze, T. L. Stemmler //Science.- 2008.-V.320.-P.1207-1210.

36. Som D. Babitt Overview of Iron Metabolism in Health and Disease / D. Som, L. Jodie // Hemodial Int. - 2017. - V. 21. - S6-S20.

37. Stys A. The role of iron regulatory proteins in the control of iron metabolism in mammals /A. Stys, R. R. Starzynski, P. Lipinski // Journal of Biotechnology, Computational Biology and Bionanotechnology. - 2011. - V. 92 (1). - P. 66-75.

38. Verga Falzacappa M. V. STAT-3 mediates hepatic hepcidin expression and its inflammatory stimulation /M. V. Verga Falzacappa, M. V. Spasic, R. Kessler //Blood. - 2007. - V. 109. -P. 353-358.

39. Volz K. The functional duality of iron regulatory protein 1 //Curr. Opin. Struct. Biol. -2008. - V. 18. - P. 106-111.

40. Wallander M. L. Molecular control of vertebrate iron homeostasis by iron regulatory proteins /M. L. Wallander, E. A. Leibold, R. S. Eisenstein //Biochim. Biophys. Acta. - 2006. - V. 1763. - P. 668-689.

41. Wang J. Regulation of cellular iron metabolism /J. Wang, K. Pantopoulos Biochem J. -2011. - V. 434. - P. 365-381.

42. Wrighting D. M. Interleukin-6 induces hepcidin expression through STAT3 /D. M. Wrighting, N. C. Andrews //Blood. - 2006. - V. 108. - P. 3204-3209.

43. Ye H. Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease /H. Ye, T. A. Rouault //Biochemistry. - 2010. - V. 49. -P. 4945-4956.

44. Yeh K. Y. Iron feeding induces ferroportin 1 and hephaestin migration and interaction in rat duodenal epithelium /K. Y. Yeh, M. Yeh, L. Mims //Am. J. Physiol. Gastrointest. Liver Physiol. - 2009. - V. 296. - G55-G65.

45. Zhang D. L. The physiological functions of iron regulatory proteins in iron homeostasis -an update /D. L. Zhang, M. C. Ghosh, T. A. Rouault //Front Pharmacol. - 2014. - P. 5-124.

46. Zhang Y. Lysosomal proteolysis is the primary degradation pathway for cytosolic ferritin and cytosolic ferritin degradation is necessary for iron exit /Y. Zhang, M. Mikhael, D. Xu //Antioxid. Redox Signaling. - 2010. - V. 13. - P. 999-1009.

47. Zhi Dong Zh. Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases / Zh. Zhi Dong, T. Eng-King //Mol. Neurodegener. - 2017. - V. 12. - P. 75. doi: 10.1186/s13024-017-0218-4.