Mechanisms of Weak Magnetic Field Influence on Gene Expression: Basics of Physical Epigenetics

1Zaporozhan, VM, 1Ponomarenko, AI
1Odessa National Medical University, Odessa
Nauka innov. 2011, 7(6):50-69
https://doi.org/10.15407/scin7.06.050
Section: Scientific Basis of Innovation Activity
Language: Russian
Abstract: 
According to the developed theory, proteins of the Cryptochrome family (CRY) are the primary magnetic field acceptor in the cell genome. These proteins are known as repressors of the major circadian transcriptional complex CLOCK/BMAL1. The mechanism described allows magnetic field to perform bioregulation functions on genome level. The magnetic field-mediated bioregulation isable to influence human health and may have epidemiological, evolutionary, climate-regulatory and ot her global consequences for biosphere.
Keywords: circadian rhythms, Cryptochrome, electromagnetic field, gene expression, NF-κB, radical pairs, transcription
References: 
1. Chizhevskij A.L. Zemnoe jeho solnechnyh bur'. 2-e ed. Moskva: Mysl', 1976 [in Russian].
2. Sage C., Carpenter D. Eds. BioInitiative Report. A Rationale for a Biologically-based Public Exposure Standard for Electromagnetic Fields (ELF and RF). 2007; Available from: www.bioinitiative.org
3. Ventura C. et al. Turning on stem cell cardiogenesis with extremely low frequency magnetic fields. FASEB J. 2005. 19(1). P. 155-157.
4. McCaig C.D. et al. Controlling cell behavior electrically: current views and future potential. Physiol. Rev. 2005. 85(3). P. 943-978.
https://doi.org/10.1152/physrev.00020.2004
5. Carpenter D.O. and C. Sage. Setting prudent public health policy for electromagnetic field exposures. Rev. Environ Health. 2008. 23(2). P. 91-117.
https://doi.org/10.1515/REVEH.2008.23.2.91
6. Mycielska M.E. and Djamgoz M.B. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J. Cell. Sci. 2004. 117(Pt 9). P. 1631-1639.
https://doi.org/10.1242/jcs.01125
7. Slack J.M. The spark of life: electricity and regeneration. Sci. STKE. 2007. 2007(405). P. 54.
https://doi.org/10.1126/stke.4052007pe54
8. Zaporozhan V.N. and Ponomarenko A.I. Evidences of regulatory and signaling role of electromagnetic fields in biological objects (review of literature and own studies). Proceedings of the 4th WSEAS Int. Conf. on Cellular and Mol. Biology, Biophysics and Bioengineering (BIO'08), Canary Islands, December 2008. P. 43-47; Available from: http://www.wseas.us/e-library/conferences/2008/tenerife/CD-BC/paper/BC07....
9. McCaig C.D., Song B. and Rajnicek A.M. Electrical dimensions in cell science. J. Cell. Sci. 2009. 122(Pt 23). P. 4267-4276.
https://doi.org/10.1242/jcs.023564
10. Zaporozhan V.N., Khait O.V. and Rebrova T.B. Shortwave therapy application in the complex treatment of bening and malignant uterine tumors. In Intnl Meeting Microwaves in medicine'91", 1991, Belgrad. P. 101-102.
11. Zaporozhan V.N., Khait O.V. and Bespoyasnaya V.V. Application of short-wave therapy in complex treatment for endometrial cancer. Eur. J. Gynaecol. Oncol. 1993. 14(4). P. 296-301.
12. Zaporozhan V.N., Bespojasna V.V., Sobolev R.V. Kombinovana z elektromagnitnym vyprominjuvannjam korekcija osnovnyh reguljatornyh system organizmu pry dobrojakisnyh puhlynah jajechnykiv. Pediatrija, akusherstvo ta ginekologija. 1997(1). P. 78-82 [in Ukrainian].
13. Lupke M. et al. Gene expression analysis of ELF-MF exposed human monocytes indicating the involvement of the alternative activation pathway. Biochim. Biophys. Acta. 2006. 1763(4). P. 402-412.
https://doi.org/10.1016/j.bbamcr.2006.03.003
14. Maercker C. In vitro gene expression studies and their im pact on high content screening assays in EMF research. in Application of Proteomics and Transcriptomics in EMF Research. 2005, Helsinki, Finland.
15. Zaporozhan V.N. ta in. Mozhlyvi mehanizmy biologichnoi' dii' geomagnitnogo polja (ogljad literatury). Eksperymental'na i klinichna medycyna. 2001. No 3. R. 153-156 [in Ukrainian].
16. Goldberg R.B. and Creasey W.A. A review of cancer induction by extremely low frequency electromagnetic fields. Is there a plausible mechanism? Med. Hypotheses. 1991. 35(3). P. 265-274.
https://doi.org/10.1016/0306-9877(91)90244-S
17. Wertheimer N. and Leeper E. Adult cancer related to electrical wires near the home. Int. J. Epidemiol. 1982. 11(4). P. 345-355.
https://doi.org/10.1093/ije/11.4.345
18. Ritz T., Adem S. and Schulten K. A model for photoreceptor-based magnetoreception in birds. Biophys. J. 2000. 78(2). P. 707-718.
https://doi.org/10.1016/S0006-3495(00)76629-X
19. Simko M. Cell type specific redox status is responsible for diverse electromagnetic field effects. Curr. Med. Chem. 2007. 14(10). P. 1141-1152.
https://doi.org/10.2174/092986707780362835
20. Fursa E.Y. Magnetic resonance as a channel of directed transmission of electromagnetic energy in animate nature, 2002.
21. Buchachenko A.L., Kuznecov D.A., Berdinskij V.L. Novye mehanizmy biologicheskih jeffektov jelektromagnitnyh polej. Biofizika. 2006. 51(3). P. 545-552 [in Russian].
22. Nagakura S.O., Hayashi H. and Azumi T. Dynamic spin chemistry: magnetic controls and spin dynamics of chemical reactions. 1998, Tokyo, New York: Kodansha; Wiley. 297 p.
23. Lednev V.V. Possible mechanism for the influence of weak magnetic fields on biological systems. Bioelectromagnetics. 1991. 12(2). P. 71-75.
https://doi.org/10.1002/bem.2250120202
24. Liboff A.R. Electric-field ion cyclotron resonance. Bioelectromagnetics. 1997. 18(1). P. 85-87.
https://doi.org/10.1002/(SICI)1521-186X(1997)18:1<85::AID-BEM13>3.0.CO;2-P
25. Fursa E.Ja. Mirozdanie — mir voln, rezonansov i nichego bolee. Minsk: UniversalPress, 2007 [in Russian].
26. Schulten K., Swenberg C.E. and Weller A. A biomagnetic sen sory mechanism based on magnetic field modulated co herent electron spin motion. Z. Phys. Chem. 1978. NF111. P. 1-5.
https://doi.org/10.1524/zpch.1978.111.1.001
27. Rodgers C.T. and Hore P.J. Chemical magnetoreception in birds: the radical pair mechanism. Proc.Natl. Acad. Sci. USA. 2009. 106(2). P. 353-360.
https://doi.org/10.1073/pnas.0711968106
28. Sagdeev R.Z. i dr. Vlijanie magnitnogo polja na radikal'nye reakcii. Pis'ma v ZhJeTF. 1972(16). P. 599-602 [in Russian].
29. Jonah C.D. and Madhava Rao B.S. Radiation chemistry: present status and future trends. 1st ed. Studies in physical and theoretical chemistry 87. 2001, Amsterdam; New York: Elsevier. 755 p.
30. Hayashi H. Introduction to dynamic spin chemistry: magnetic field effects on chemical and biochemical re actions, in World scientific lecture and course notes in chemistry. Vol. 8. 2004, World Scientific: River Edge, N.J.
31. Eichwald C. and Walleczek J. Model for magnetic field effects on radical pair recombination in enzyme kinetics. Biophys. J. 1996. 71(2). P. 623-631.
https://doi.org/10.1016/S0006-3495(96)79263-9
32. Izmaylov A.F., Tully J.C. and Frisch M.J. Relativistic interactions in the radical pair model of magnetic field sense in CRY-1 protein of Arabidopsis thaliana. J. Phys. Chem. A. 2009. 113(44). P. 12276-12284.
https://doi.org/10.1021/jp900357f
33. Brocklehurst B. Magnetic fields and radical reactions: recent developments and their role in nature. Chem. Soc. Rev. 2002. 31(5). P. 301-311.
https://doi.org/10.1039/b107250c
34. Ahmad M. et al. Magnetic intensity affects cryptochromedependent responses in Arabidopsis thaliana. Planta. 2007. 225(3). P. 615-624.
https://doi.org/10.1007/s00425-006-0383-0
35. Harris S.R. et al. Effect of magnetic fields on cryptochrome-dependent responses in Arabidopsis thaliana. J. R. Soc. Interface, 2009. 6(41). P. 1193-11205.
https://doi.org/10.1098/rsif.2008.0519
36. Lin C. and Todo T. The cryptochromes. Genome Biol. 2005. 6(5). P. 220.
https://doi.org/10.1186/gb-2005-6-5-220
37. Brudler R. et al. Identification of a new cryptochrome class. Structure, function, and evolution. Mol. Cell. 2003. 11(1). P. 59-67.
https://doi.org/10.1016/S1097-2765(03)00008-X
38. Partch C.L. and Sancar A. Photochemistry and photobiology of cryptochrome blue-light photopigments: the search for a photocycle. Photochem Photobiol. 2005. 81(6). P. 1291-1304.
https://doi.org/10.1562/2005-07-08-IR-607
39. Solov'yov I.A. and Schulten K. Magnetoreception through cryptochrome may involve superoxide. Biophys. J. 2009. 96(12). P. 4804-4813.
https://doi.org/10.1016/j.bpj.2009.03.048
40. Zhu H., Conte F. and Green C.B. Nuclear localization and transcriptional repression are confined to separable domains in the circadian protein CRYPTOCHROME. Curr. Biol. 2003. 13(18). P. 1653-1658.
https://doi.org/10.1016/j.cub.2003.08.033
41. Chaves I. et al. Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance. Mol. Cell. Biol. 2006. 26(5). P. 1743-1753.
https://doi.org/10.1128/MCB.26.5.1743-1753.2006
42. Allada R. et al. Stopping time: the genetics of fly and mouse circadian clocks. Annu. Rev. Neurosci. 2001. 24. P. 1091-1119.
https://doi.org/10.1146/annurev.neuro.24.1.1091
43. Cashmore A.R. Cryptochromes: enabling plants and animals to determine circadian time. Cell. 2003. 114(5). P. 537-543.
https://doi.org/10.1016/j.cell.2003.08.004
44. Kaushik R. et al., PER-TIM interactions with the photoreceptor cryptochrome mediate circadian temperature responses in Drosophila. PLoS Biol. 2007. 5(6). P. 1257-1266.
https://doi.org/10.1371/journal.pbio.0050146
45. Panda S. and Hogenesch J.B. It's all in the timing: many clocks, many outputs. J. Biol. Rhythms. 2004. 19(5). P. 374-387.
https://doi.org/10.1177/0748730404269008
46. Langmesser S. et al. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK. BMC Mol Biol. 2008. 9. P. 41.
https://doi.org/10.1186/1471-2199-9-41
47. Etchegaray J.P. et al. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature. 2003. 421(6919). P. 177-182.
https://doi.org/10.1038/nature01314
48. Kondratov R.V. et al. Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation. FASEB J. 2006. 20(3). P. 530-532.
https://doi.org/10.1096/fj.05-5321fje
49. Reiter R.J. Static and extremely low frequency electromagnetic field exposure: reported effects on the circadian production of melatonin. J. Cell. Biochem. 1993. 51(4). P. 394-403.
https://doi.org/10.1002/jcb.2400510403
50. Choi Y.M. et al. Extremely low frequency magnetic field exposure modulates the diurnal rhythm of the pain threshold in mice. Bioelectromagnetics. 2003. 24(3). P. 206-210.
https://doi.org/10.1002/bem.10094
51. Goodman R. et al. Transcription in Drosophila melanogaster salivary gland cells is altered following exposure to lowfrequency electromagnetic fields: analysis of chromosome 3R. Bioelectromagnetics. 1992. 13(2). P. 111-118.
https://doi.org/10.1002/bem.2250130205
52. Litovitz T.A. et al. Amplitude windows and transiently augmented transcription from exposure to electromagnetic fields. Bioelectromagnetics. 1990. 11(4). P. 297-312.
https://doi.org/10.1002/bem.2250110406
53. Wei L.X., Goodman R., and Henderson A., Changes in levels of c-myc and histone H2B following exposure of cells to low-frequency sinusoidal electromagnetic fields: evidence for a window effect. Bioelectromagnetics. 1990. 11(4). P. 269-272.
https://doi.org/10.1002/bem.2250110403
54. Hirai T. and Yoneda Y. Transcriptional regulation of neuronal genes and its effect on neural functions: gene expression in response to static magnetism in cultured rat hippocampal neurons. J. Pharmacol. Sci. 2005. 98(3). P. 219-224.
https://doi.org/10.1254/jphs.FMJ05001X5
55. Barnes F.S. and Greenebaum B. Handbook of biological effects of electromagnetic fields. Bioengineering and biophysical aspects of electromagnetic fields. 3rd ed. 2007, Boca Raton, FL: CRC/Taylor & Francis. [xxxvi]. 440 p.
56. Mellstrom B. and Naranjo J.R. Mechanisms of Ca(2+)-dependent transcription. Curr Opin Neurobiol. 2001. 11(3). P. 312-319.
https://doi.org/10.1016/S0959-4388(00)00213-0
57. Mellstrom B. et al. Ca2+-operated transcriptional networks: molecular mechanisms and in vivo models. Physiol. Rev. 2008. 88(2). P. 421-449.
https://doi.org/10.1152/physrev.00041.2005
58. Bootman M.D. et al. An update on nuclear calcium signalling. J. Cell. Sci. 2009. 122(Pt 14). P. 2337-2350.
https://doi.org/10.1242/jcs.028100
59. Savignac M., Mellstrom B., and Naranjo J.R. Calcium-dependent transcription of cytokine genes in T lymphocytes. Pflugers Arch. 2007. 454(4). P. 523-533.
https://doi.org/10.1007/s00424-007-0238-y
60. Nuccitelli S. et al. Hyperpolarization of plasma membrane of tumor cells sensitive to antiapoptotic effects of magnetic fields. Ann. N-Y Acad. Sci. 2006. 1090. P. 217-225.
https://doi.org/10.1196/annals.1378.024
61. Cho M.R. et al. Transmembrane calcium influx induced by acelectric fields. FASEB J. 1999. 13(6). P. 677-683.
62. Chionna A.D.M. et al. Cell shape and plasma membrane alterations after static magnetic fields exposure. Eur. J. Histochem. 2003. 47(4). P. 299-308.
63. Blackman C.F. et al. Effects of ELF (1-120 Hz) and modulated (50 Hz) RF fields on the efflux of calcium ions from brain tissue in vitro. Bioelectromagnetics. 1985. 6(1). P. 1-11.
https://doi.org/10.1002/bem.2250060102
64. Liboff A.R. Electric polarization and the viability of living systems: ion cyclotron resonance-like interactions. Electromagn. Biol. Med. 2009. 28(2). P. 124-134.
https://doi.org/10.1080/15368370902729293
65. Flipo D. et al. Increased apoptosis, changes in intracellular Ca2+, and functional alterations in lymphocytes and macrophages after in vitro exposure to static magnetic field. J. Toxicol. Environ. Health A. 1998. 54(1). P. 63-76.
https://doi.org/10.1080/009841098159033
66. Conti P. et al. A role for Ca2+ in the effect of very low fre quency electromagnetic field on the blastogenesis of human lymphocytes. FEBS Lett. 1985. 181(1). P. 28-32.
https://doi.org/10.1016/0014-5793(85)81107-8
67. Walleczek J. Electromagnetic field effects on cells of the immune system: the role of calcium signaling. FASEB J. 1992. 6(13). P. 3177-3185.
69. Bonizzi G. and Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends. Immunol. 2004. 25(6). P. 280-288.
https://doi.org/10.1016/j.it.2004.03.008
70. Hayden M.S. and Ghosh S. Signaling to NF-kappaB. Ge nes. Dev. 2004. 18(18). P. 2195-2224.
https://doi.org/10.1101/gad.1228704
71. Bozek, K. et al. Promoter analysis of Mammalian clock con trolled genes. Genome Inform. 2007. 18. P. 65-74.
72. Nader N., Chrousos G.P. and Kino T. Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J. 2009. 23(5). P. 1572-1583.
https://doi.org/10.1096/fj.08-117697
73. McKay L.I. and Cidlowski J.A. CBP (CREB binding protein) integrates NF-kappaB (nuclear factor-kappaB) and glucocorticoid receptor physical interactions and antagonism. Mol. Endocrinol. 2000. 14(8). P. 1222-1234.
74. Nikolova T. et al. Electromagnetic fields affect transcript levels of apoptosis-related genes in embryonic stem cellderived neural progenitor cells. FASEB J. 2005. 19(12). P. 1686-1688.
75. Delle Monache S. et al. Extremely low frequency electromagnetic fields (ELF-EMFs) induce in vitro angiogenesis process in human endothelial cells. Bioelectromagnetics. 2008. 29(8). P. 640-648.
https://doi.org/10.1002/bem.20430
76. Goodman R. et al. Extremely low frequency electro magnetic fields activate the ERK cascade, increase hsp70 protein levels and promote regeneration in Planaria. Int. J. Radiat Biol. 2009. P. 1-9.
77. Maercker C. Do electromagnetic fields induce stress response? A whole-genome approach helps to identify cellular pathways modulated by electromagnetic fields in Application of Proteomics and Transcriptomics in EMF Research. 2005, Helsinki, Finland.
78. Simko M. and Mattsson M.O. Extremely low frequency electromagnetic fields as effectors of cellular responses in vitro: possible immune cell activation. J. Cell. Biochem. 2004. 93(1). P. 83-92.
https://doi.org/10.1002/jcb.20198
79. Bonhomme-Faivre L. et al. Alterations of biological parameters in mice chronically exposed to low-frequency (50 Hz) electromagnetic fields. Life Sci. 1998. 62(14). P. 1271-1280.
https://doi.org/10.1016/S0024-3205(98)00057-5
80. Bonhomme-Faivre L. et al. Study of human neurovegetative and hematologic effects of environmental low-frequency (50-Hz) electromagnetic fields produced by transformers. Arch. Environ. Health. 1998. 53(2). P. 87-92.
https://doi.org/10.1080/00039896.1998.10545968
81. Frahm, J. et al. Alteration in cellular functions in mouse macrophages after exposure to 50 Hz magnetic fields. J Cell Biochem. 2006. 99(1). P. 168-177.
https://doi.org/10.1002/jcb.20920
82. Pikarsky E. and Ben-Neriah Y. NF-kappaB inhibition: a double-edged sword in cancer? Eur. J. Cancer. 2006. 42(6). P. 779-784.
https://doi.org/10.1016/j.ejca.2006.01.011
83. Li Q., Withoff S. and Verma I.M., Inflammation-associated cancer: NF-kappaB is the lynchpin. Trends. Immunol. 2005. 26(6). P. 318-325.
https://doi.org/10.1016/j.it.2005.04.003
84. Solar Cycle Progression Space Weather Prediction Center (NOAA/SWPC) 2009; Available from: http://www.swpc.noaa.gov/SolarCycle/