The effect of antipsychotic therapy to the ribosomal repeat copy number variation in the the composition of plasma circulating DNA in patients with schizophrenia
https://doi.org/10.25557/2073-7998.2023.05.40-53
Abstract
Circulating extracellular DNA (cfDNA) in pathology has a negative effect on the cells of the body, supporting systemic inflammation. Ribosomal repeat fragments (rDNA), which accumulate in cfDNA, activate the transcription factor NF-kB, which regulates the transcription of pro-inflammatory cytokine genes. The work shows that antipsychotic therapy is associated with a significant decrease in the concentration of biologically active rDNA fragments in the blood plasma of patients. The search for low-toxic synthetic and natural compounds based on the molecular structures that make up antipsychotics may lead to the emergence of drugs that change the biological activity of cfDNA.
Supporting agencies: The work was supported by the state task of the Ministry of Science and Higher Education for Research Centre for Medical Genetics.
About the Authors
E. S. Ershova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechye st., Moscow, 115522
E. M. Jestkova
Psychiatric Hospital No. 4 of Moscow City Health Department
Russian Federation
Russian Federation
3, Poteshnaya st., Moscow, 115447
A. V. Martynov
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechye st., Moscow, 115522
N. V. Zakharova
Psychiatric Hospital no. 1 Named after N.A. Alexeev of the Department of Health of Moscow
Russian Federation
Russian Federation
2, Zagorodnoye shosse, Moscow, 115447
L. V. Bravve
Psychiatric Hospital no. 1 Named after N.A. Alexeev of the Department of Health of Moscow
Russian Federation
Russian Federation
2, Zagorodnoye shosse, Moscow, 115447
G. P. Kostyuk
Psychiatric Hospital no. 1 Named after N.A. Alexeev of the Department of Health of Moscow
Russian Federation
Russian Federation
2, Zagorodnoye shosse, Moscow, 115447
N. N. Veiko
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechye st., Moscow, 115522
S. V. Kostyuk
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechye st., Moscow, 115522
References
1. Wan J.C.M., Massie C., Garcia-Corbacho J., Mouliere F., Brenton J.D., Caldas C., Pacey S., Baird R., Rosenfeld N. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-238. doi: 10.1038/nrc.2017.7.
2. Heitzer E., Haque I.S., Roberts C.E.S., Speicher M.R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20(2):71-88. doi: 10.1038/s41576-018-0071-5.
3. Kustanovich A., Schwartz R., Peretz T., Grinshpun A. Life and death of circulating cell-free DNA. Cancer Biol Ther. 2019;20(8):1057-1067. doi: 10.1080/15384047.2019.1598759.
4. Duvvuri B., Lood C. Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Front Immunol. 2019;10:502. doi: 10.3389/fimmu.2019.00502.
5. Han D.S.C., Lo Y.M.D. The Nexus of cfDNA and Nuclease Biology. Trends Genet. 2021;37(8):758-770. doi: 10.1016/j.tig.2021.04.005.
6. Knight SR, Thorne A, Lo Faro ML. Donor-specific Cell-free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review. Transplantation. 2019;103(2):273-283. doi: 10.1097/TP.0000000000002482.
7. Meddeb R., Dache Z.A.A., Thezenas S., Otandault A., Tanos R., Pastor B., Sanchez C., Azzi J., Tousch G., Azan S., Mollevi C., Adenis A., El Messaoudi S., Blache P., Thierry A.R. Quantifying circulating cell-free DNA in humans. Sci Rep. 2019;9(1):5220. doi: 10.1038/s41598-019-41593-4.
8. Marsman G., Zeerleder S., Luken B.M. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation. Cell Death Dis. 2016;7(12):e2518. doi: 10.1038/cddis.2016.410.
9. Nie L., Cai S.Y., Shao J.Z, Chen J. Toll-Like Receptors, Associated Biological Roles, and Signaling Networks in Non-Mammals. Front Immunol. 2018;9:1523. doi: 10.3389/fimmu.2018.01523.
10. Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104-7. doi: 10.1038/nature08780.
11. Dwivedi D.J., Toltl L.J., Swystun L.L., Pogue J., Liaw K.L., Weitz J.I., Cook D.J., Fox-Robichaud A.E., Liaw P.C.; Canadian Critical Care Translational Biology Group. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis. Crit Care. 2012;16(4):R151. doi: 10.1186/cc11466.
12. Weber C., Jenke A., Chobanova V., Yazdanyar M., Chekhoeva A., Eghbalzadeh K., Lichtenberg A, Wahlers T, Akhyari P, Paunel-Görgülü A. Targeting of cell-free DNA by DNase I diminishes endothelial dysfunction and inflammation in a rat model of cardiopulmonary bypass. Sci Rep. 2019;9(1):19249. doi: 10.1038/s41598-019-55863-8.
13. Soni C., Reizis B. DNA as a self-antigen: nature and regulation. Curr Opin Immunol. 2018;55:31-37. doi: 10.1016/j.coi.2018.09.009.
14. Chan R.W., Jiang P., Peng X., Tam L.S., Liao G.J., Li E.K., Wong P.C., Sun H., Chan K.C., Chiu R.W., Lo Y.M. Plasma DNA aberrations in systemic lupus erythematosus revealed by genomic and methylomic sequencing. Proc Natl Acad Sci U S A. 2014;111(49):E5302-11. doi: 10.1073/pnas.1421126111.
15. Tamkovich S.N., Cherepanova A.V., Kolesnikova E.V., Rykova E.Y., Pyshnyi D.V., Vlassov V.V., Laktionov P.P. Circulating DNA and DNase activity in human blood. Ann N Y Acad Sci. 2006;1075:191-6. doi: 10.1196/annals.1368.026.
16. Kawai Y., Yoshida M., Arakawa K., Kumamoto T., Morikawa N., Masamura K., Tada H., Ito S., Hoshizaki H., Oshima S., Taniguchi K., Terasawa H., Miyamori I., Kishi K., Yasuda T. Diagnostic use of serum deoxyribonuclease I activity as a novel early-phase marker in acute myocardial infarction. Circulation. 2004;109(20):2398-400. doi: 10.1161/01.CIR.0000129232.61483.43.
17. Yasuda T., Iida R., Kawai Y., Nakajima T., Kominato Y., Fujihara J., Takeshita H. Serum deoxyribonuclease I can be used as a useful marker for diagnosis of death due to ischemic heart disease. Leg Med (Tokyo). 2009;11 Suppl 1:S213-5. doi: 10.1016/j.legalmed.2009.01.092.
18. Ershova E., Sergeeva V., Klimenko M., Avetisova K., Klimenko P., Kostyuk E., Veiko N., Veiko R., Izevskaya V., Kutsev S., Kostyuk S. Circulating cell-free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy. Biomed Rep. 2017;7(4):319-324. doi: 10.3892/br.2017.968.
19. Velders M., Treff G., Machus K., Bosnyák E., Steinacker J., Schumann U. Exercise is a potent stimulus for enhancing circulating DNase activity. Clin Biochem. 2014;47(6):471-4. doi: 10.1016/j.clinbiochem.2013.12.017.
20. Veiko N.N., Shubaeva N.O., Ivanova S.M., Speransky A.I., Lyapunova N.A., Spitkovsky D.M. DNK syvorotki krovi bol’nykh revmatoidnym artritom znachitel’no obogashchena fragmentami ribosomnykh povtorov, soderzhashchikh immunostimuliruyushchiye CpG–motivy [Serum DNA of patients with rheumatoid arthritis is significantly enriched in fragments of ribosomal repeats containing immunostimulatory CpG motifs]. Byulleten’ eksperimental’noy biologii i meditsiny [Bulletin of Experimental Biology and Medicine]. 2006; 9:282-285. (In Russ.)
21. Korzeneva I.B., Kostuyk S.V., Ershova E.S., Skorodumova E.N., Zhuravleva VF, Pankratova GV, Volkova IV, Stepanova EV, Porokhovnik LN, Veiko NN. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation. Mutat Res. 2016;791-792:49-60. doi: 10.1016/j.mrfmmm.2016.09.001.
22. Veiko N.N., Bulycheva N.A., Roginko O.A., Veiko R.V., Ershova E.S., Kozdoba O.A., Kuzmin V.A., Vinogradov A.M., Yudin A.A., Speranskyi A.I. Fragmenty transkribiruyemoy oblasti ribosomnogo povtora v sostave vnekletochnoy DNK — marker gibeli kletok organizma [Ribosomal repeat in the cell free DNA as a marker for cell death]. Biomeditsinskaya Khimiya [Biomedical Chemistry]. 2008; 54(1):78-93. (In Russ.)
23. Aswani A., Manson J., Itagaki K., Chiazza F., Collino M., Wupeng W.L., Chan T.K., Wong W.S.F., Hauser C.J., Thiemermann C., Bro-hi K. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage. Front Immunol. 2018;9:891. doi: 10.3389/fimmu.2018.00891.
24. Ershova E.S., Jestkova E.M., Martynov A.V., Shmarina G.V., Umriukhin P.E., Bravve L.V., Zakharova N.V., Kostyuk G.P., Saveliev D.V., Orlova M.D., Bogush M., Kutsev S.I., Veiko N.N., Kostyuk S.V. Accumulation of Circulating Cell-Free CpG-Enriched Ribosomal DNA Fragments on the Background of High Endonuclease Activity of Blood Plasma in Schizophrenic Patients. Int J Genomics. 2019;2019:8390585. doi: 10.1155/2019/8390585.
25. Ershova E.S., Jestkova E.M., Chestkov I.V., Porokhovnik L.N., Izevskaya V.L., Kutsev S.I., Veiko N.N., Shmarina G., Dolgikh O., Kostyuk S.V. Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients. J Psychiatr Res. 2017;87:15-22. doi: 10.1016/j.jpsychires.2016.12.006.
26. Jung M., Kristiansen G., Dietrich D. DNA Methylation Analysis of Free-Circulating DNA in Body Fluids. Methods Mol Biol. 2018;1708:621-641. doi: 10.1007/978-1-4939-7481-8_32.
27. Jiang J., Chen X., Sun L., Qing Y., Yang X., Hu X., Yang C., Xu T., Wang J., Wang .P, He L., Dong C., Wan C. Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy. Transl Psychiatry. 2018;8(1):104. doi: 10.1038/s41398-018-0153-3.
28. Qi J., Chen L.Y., Shen X.J., Ju .SQ. Analytical Value of Cell-Free DNA Based on Alu in Psychiatric Disorders. Front Psychiatry. 2020;10:992. doi: 10.3389/fpsyt.2019.00992.
29. Ouyang H., Huang M., Xu Y., Yao Q., Wu X., Zhou D. Reduced Cell-Free Mitochondrial DNA Levels Were Induced by Antipsychotics Treatment in First-Episode Patients With Schizophrenia. Front Psychiatry. 2021;12:652314. doi: 10.3389/fpsyt.2021.652314.
30. Ershova E.S., Shmarina G.V., Porokhovnik L.N., Zakharova N.V., Kostyuk G.P., Umriukhin P.E., Kutsev S.I., Sergeeva V.A., Veiko N.N., Kostyuk S.V. In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls. Genes (Basel). 2022;13(3):551. doi: 10.3390/genes13030551.
31. Chestkov I.V., Jestkova E.M., Ershova E.S., Golimbet V.E., Lezheiko T.V., Kolesina N.Y., Porokhovnik L.N., Lyapunova N.A., Izhevskaya V.L., Kutsev .SI., Veiko N.N., Kostyuk S.V. Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients. Schizophr Res. 2018;197:305-314. doi: 10.1016/j.schres.2018.01.001.
32. Jestkova E.M., Ershova E.S., Martynov A.V., Zakharova N.V., Kostyuk G.P., Veiko N.N., Kostyuk S.V. Kontsentratsiya tsirkuliruyushchey vnekletochnoy DNK v plazme perifericheskoy krovi bol’nykh s ostrymi psikhozami endogennoy i ekzogennoy etiologii [Concentration of Circulating Cell-Free DNA in the Peripheral Blood Plasma of Patients with Acute Endogenous and Exogenous Etiology Psychoses]. Psikhiatriya [Psikhiatriya]. 2021;19(3):6-14. (In Russ.) https://doi.org/10.30629/2618-6667-2021-19-3-6-14
33. Kostyuk S.V. Rol’ vnekletochnoy DNK v funktsional’noy aktivnosti genoma cheloveka. Dissertatsiya …. doktora biologicheskikh nauk [The role of extracellular DNA in the functional activity of the human genome. Thesis…. Doctor of Biological Sciences]. Moscow, 2014.- 450 p. (In Russ.)
34. Kumar R., Sonkar V.K., Swamy J., Ahmed A., Sharathkumar A.A., Pierce G.L., Dayal S. DNase 1 Protects From Increased Thrombin Generation and Venous Thrombosis During Aging: Cross-Sectional Study in Mice and Humans. J Am Heart Assoc. 2022;11(2):e021188. doi: 10.1161/JAHA.121.021188.
35. Dawulieti J., Sun M., Zhao Y., Shao D., Yan H., Lao Y.H., Hu H., Cui L., Lv X., Liu F., Chi C.W., Zhang Y., Li M., Zhang M., Tian H., Chen X., Leong K.W., Chen L. Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers. Sci Adv. 2020;6(22):eaay7148. doi: 10.1126/sciadv.aay7148.
36. Liang H., Peng B., Dong C., Liu L., Mao J., Wei S., Wang X., Xu H., Shen J., Mao H.Q., Gao X., Leong K.W., Chen Y. Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation. Nat Commun. 2018;9(1):4291. doi: 10.1038/s41467-018-06603-5.
37. Liu F., Sheng S., Shao D., Xiao Y., Zhong Y., Zhou J., Quek C.H., Wang Y., Hu Z., Liu H., Li Y., Tian H., Leong K.W., Chen X. A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management. Nano Lett. 2021;21(6):2461-2469. doi: 10.1021/acs.nanolett.0c04759.
38. Chen Y., Wang Y., Jiang X., Cai J., Chen Y., Huang H., Yang Y., Zheng L., Zhao J., Gao M. Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy. Bioact Mater. 2022;18:409-420. doi: 10.1016/j.bioactmat.2022.03.028.
Review
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Ershova E.S., Jestkova E.M., Martynov A.V., Zakharova N.V., Bravve L.V., Kostyuk G.P., Veiko N.N., Kostyuk S.V. The effect of antipsychotic therapy to the ribosomal repeat copy number variation in the the composition of plasma circulating DNA in patients with schizophrenia. Medical Genetics. 2023;22(5):40-53. (In Russ.) https://doi.org/10.25557/2073-7998.2023.05.40-53
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