Omic markers identification for predicting risks of negative effects in children with elevated copper and nickel contents in blood

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UDC: 
612.12: 616.092
DOI: 
10.21668/health.risk/2021.1.05.eng
Authors: 

N.V. Zaitseva1, M.A. Zemlyanova1,2, Yu.V. Koldibekova1, N.I. Bulatova1

Organization: 

1Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation
2Perm State University, 15 Bukireva Str., Perm, 614990, Russian Federation

Abstract: 

Proteomic profiling is a promising procedure for examining and substantiating molecular mechanisms of body reactions occurrence and development as a response to adverse impacts; it allows detecting and examining these reactions at early stages in their development prior to cellular damage and damage to organs. Studies aimed at increasing efficiency of adverse effects prediction are especially vital for solving tasks related to early detection and prevention of consequences associated with exposure to chemical environmental factors, first of all, ambient air.
Our research goal was to identify omic-markers for predicting risks of negative effects in children with elevated copper and nickel contents in blood.
We performed proteomic blood plasma examination in children and modeled cause-and-effect relations. Children with copper and nickel contents in their blood being 3.5 times higher than physiological standard had approximately 20 protein stains that were authentically different from those detected in children from the reference group. We detected correlations between an increase in relative volume of three protein stains including apolipoprotein A-I, anchor protein of A-kinase 9, vitronectin, and a decrease in relative volume of one protein strain including transthyretin and elevated copper and nickel contents in blood (R2=0.30–0.44; р=0.0001–0.008). All the above-mentioned proteins have predictive significance when it comes down to negative effects related to neuroregulation disorders and endothelial dysfunction. It was proven that there was a risk of predicted negative effects such as greater frequency of nervous and cardiovascular system diseases in case copper and nickel contents in blood were elevated (R2=0.35–0.96; р=0.0001–0.013). The established list of potential target molecules (apolipoprotein A-I, vitronectin, anchor protein of A-kinase 9, and transthyretin) and genes that coded their expression (APOA1, VTN,AKAP9,TTR) was substantiated as omic-markers indicating a possibility that negative effects might occur in the cardiovascular and nervous system.

Keywords: 
copper and nickel in blood, health risk, proteomic profile of blood plasma, nervous system, cardiovascular system, apolipoprotein A-I, anchor protein of А-kinase 9, vitronectin, transthyretin
Zaitseva N.V., Zemlyanova M.A., Koldibekova Yu.V., Bulatova N.I. Omic markers identification for predicting risks of negative effects in children with elevated copper and nickel contents in blood. Health Risk Analysis, 2021, no. 1, pp. 48–56. DOI: 10.21668/health.risk/2021.1.05.eng
References: 
  1. Barbarini N., Magni P. Accurate peak list extraction from proteomic mass spectra for identification and profiling studies. BMC. Bioinformatics, 2010, vol. 11, no. 518, pp. 1–14. DOI: 10.1186/1471-2105-11-518
  2. Shenderov B.A. «Omik»-tekhnologii i ikh znachenie v sovremennoi profilakticheskoi i vosstanovitel'noi meditsine [«Omic»-technologies and their significance for contemporary preventive and recovery medicine]. Vestnik vosstanovitel'noi meditsiny, 2012, no. 3, pp. 7078 (in Russian).
  3. Polunina T.A., Varshavskaya Yu.S., Grigor'eva G.V., Krasnov Ya.M. Proteomic methods of protein separation and analysis. Zhurnal mikrobiologii, epidemiologii i immunobiologii, 2014, no. 3, pp. 107–114 (in Russian).
  4. Ahn S.-M., Simpson R.J. Body fluid proteomics: Prospects for biomarker discovery. Proteomics Clin. Appl, 2007, vol. 1, no. 9, pp. 1004–1015. DOI: 10.1002/prca.200700217
  5. Larina I.M., Ivanisenko V.A., Nikolaev E.N., Grigorev A.I. The proteome of a healthy human during physical activity under extreme conditions (Reviews). Actа Naturae, 2014, vol. 6, no. 3 (22), pp. 66–75.
  6. Aebersold R., Agar J., Amster I., Baker M.S., Bertozzi C.R., Boja E.S., C.E. Costello, B.F. Cravatt [et al.]. How many human proteoforms are there? Nature chemical biology, 2018, vol. 14, no. 3, pp. 206–214. DOI: 10.1038/nchembio.2576
  7. PROTEAN i12 IEF System. Instruction Manual. Hercules, Bio-Rad Laboratories, Inc Publ., 2011, 60 p.
  8. PROTEAN II xi 2D cell. Instruction Manual. Hercules, Bio-Rad Laboratories, Inc Publ., 2011, 52 p.
  9. ReadyPrep 2-D starter Kit. Instruction manual. Hercules, Bio-Rad Laboratories, Inc Publ., 2011, 28 p.
  10. Wu S., Deng F., Wei H., Huang J., Wang H., Shima M., Wang X., Qin Y. [et al.]. Chemical constituents of ambient particulate air pollution and biomarkers of in flammation, coagulation and homocysteine in healthy adults: a prospective panel study. Part. Fibre Toxicol, 2012, vol. 9, no. 49, pp. 1–13. DOI: 10.1186/1743-8977-9-49
  11. Knyazev R.A., Trifonova N.V., Ryabchenko A.V., Kotova M.V., Kolpakov A.R., Polyakov L.M. Impact of recombinant apolipoprotein A-I on myocardial function in experiment. Patologiya krovoobrashcheniya i kardiokhirurgiya, 2018, no. 22 (4), pp. 88–94 (in Russian).
  12. Maranhão R.C., Freitas F.R. HDL Metabolism and Atheroprotection: Predictive Value of Lipid Transfers. Advances in Clinical Chemistry, 2014, no. 65, pp. 1–41. DOI: 10.1016/B978-0-12-800141-7.00001-2
  13. Chumakova G.A., Gritsenko O.V., Veselovskaya N.G., Vakhromeeva E.V., Kozarenko A.A. Clinical role of apolipoproteins A and B. Kardiovaskulyarnaya terapiya i profilaktika, 2011, vol. 10, no. 6, pp. 105–111 (in Russian).
  14. Masaharu H., Takeshi Y., Katsuko N., Ai S.-N., Tomoko F., Yuichi M., Takaya G., Katsushi T. Vitronectin improves cell survival after radiation injury in human umbilical vein endothelial cells. FEBS Open Bio, 2012, no. 2, pp. 334–338. DOI: 10.1016/j.fob.2012.10.002
  15. Ruggeri Z.M., Jackson S.P. Platelet Thrombus Formation in Flowing Blood. Platelet biology, 2013, no. 2, pp. 399–423. DOI: 10.1016/B978-0-12-387837-3.00020-1
  16. Konstantinides S., Schafer K., Thinnes T., Loskutoff D.J. Plasminogen activator inhibitor-1 and its cofactor vitronectin stabilize arterial thrombi after vascular injury in mice. Circulation, 2001, no. 103, pp. 576–583. DOI: 10.1161/01.cir.103.4.576
  17. Sarnat S.E., Winquist A., Schauer J.J., Turner J.R., Sarnat J.A. Fine particulate matter components and emergency department visits for cardiovascular and respiratory diseases in the St. Louis, Missouri-Illinois, Metropolitan Area. Environ. Health Perspect, 2015, vol. 5, no. 123, pp. 437–444. DOI: 10.1289/ehp.1307776
  18. Kolpakova A.F., Sharipov R.N., Kolpakov F.A. Air pollution by particulate matter as the risk factor for the cardiovascular diseases. Gigiena i sanitariya, 2017, vol. 96, no. 2, pp. 133–137 (in Russian).
  19. Liu Yu., Merrill R.A., Strack S. A-Kinase Anchoring Protein 1: Emerging Roles in Regulating Mitochondrial Form and Function in Health and Disease (Review). Cells, 2020, vol. 9, no. 298, pp. 2–12. DOI: 10.3390/cells9020298
  20. Flippo K.H., Gnanasekaran A., Perkins G.A., Ajmal A., Merrill R.A., Dickey A.S., Taylor S.S., McKnight G.S. [et al.]. AKAP1 Protects from Cerebral Ischemic Stroke by Inhibiting Drp1-Dependent Mitochondrial Fission. J. Neurosci, 2018, vol. 19, no. 38, pp. 8233–8242. DOI: 10.1523/JNEUROSCI.0649-18.2018
  21. Remaud S., Gothié J.-D., Morvan-Dubois G., Demeneix B.A. Thyroid hormone signaling and adult neurogenesis in mammals. Front. Endocrinol, 2014, vol. 5, no. 62, pp. 1–7. DOI: 10.3389/fendo.2014.00062
  22. V'yunova T.V., Medvedeva E.V., Andreeva L.A., Dergunova L.V., Limborskaya S.A., Myasoedov N.F. A possible role of transthyretin in the biological mechanism of regulatory peptide neuroprotection. Molekulyarnaya genetika, mikrobiologiya i virusologiya, 2016, vol. 34, no. 3, pp. 104–109 (in Russian).
  23. Brouillette J., Quirion R. Transthyretin: a key gene involved in the maintenance of memory capacities during aging. Neurobiol. Aging, 2008, vol. 29, no. 11, pp. 1721–1732. DOI: 10.1016/j.neurobiolaging.2007.04.007
Received: 
12.01.2021
Accepted: 
15.03.2021
Published: 
30.03.2021

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