Study of RBCs membrane proteins and defining their potential biomarker role for tumourigenesis monitoring
G. Sharashenidze
, E. Tikaradze
, E. Shekiladze
, M. Mantskava
, N. Momtselidze
, N. Kipiani
, M. Tsimakuridze
, G. Ormotsadze
, T. Sanikidze
, N. Antonova
Abstract: Assessment of the causal relationship between ecological stress levels and the frequency of chronic oncological pathologies, developing new effective predictive markers of individual and population risk of population morbidity and identifying specific and non-specific mechanisms of individual and population sensitivity to external factors is one of the priority areas of modern medicine. Investigation of new potential biomarkers (erythrocyte membrane proteins characteristics) of virtually healthy residents of the ethnically homogeneous population for monitoring the cancer morbidity in the Sachkhere district as one of the most favourable regions (in terms of the territorial-economic, ecologic and geographic situation) of Georgia. The healthy volunteers from different villages (Chorvila, Sairkhe, Sareki) of Sachkhere District randomly were included in the study. Exclusion criteria were malignant tumours, nicotine users, excessive alcohol users, and severe chronic diseases. The spectrophotometric absorption of red blood cell (RBC) membrane proteins, their electrophoresis, glycophorin A expression level, and blood test clinical values in groups of volunteers from the different villages were investigated. The spectrophotometric absorption in RBCs’ membrane proteins at 230nm was 14% higher and the level of dimerized Glycophorin A statistically significantly decreased by 15-20% in Sareki's inhabitants than in the inhabitants of Sairkhe and Chorvila. There were no statistically significant changes in the number of erythrocytes, platelets, leukocytes, lymphocytes, neutrophils, and haemoglobin; anisotropy of RBC distribution width (RDW) (variation in RBC volume and size), was found – in residents of Sareki it was higher than in Sairkhe and Chorvila. Each of the studied indicators belongs to the class of pleiotropic markers, only their complexity can be considered as an early predictor of oncological risk.
Series on Biomechanics, Vol.37, No.3 (2023), 68-79
Keywords: biomarker; Glycophorin A; RBC membrane proteins; Tumourigenesis
| References: (click to open/close) | [1] Bhatt. A.N, Mathur, R., Farooque, A., Verma, A., Dwarakanath, B.S., 2010. Cancer biomarkers - Current perspectives. Indian J Med Res. 132, 129-149. PMID: 20716813.
[2] Martinez, E., Achcar J., 2014. Trends in epidemiology in the 21st century: time to adopt Bayesian methods. Saude Publica. 30, 4, 703-14. DOI: 10.1590/0102-311x00144013.
[3] Lioy, P., Smith, K., 2013. A Discussion of Exposure Science in the 21st Century: A Vision and a Strategy Environmental Health Perspectives, 121, 4, 405-409. DOI: 10.1289/ehp.1206170.
[4] Tikaradze, E., Sharashenidze, G., Ormotsadze, G., Tsimakuridze, M., Burjanadze, G., Chkhikvishvili I., Kalmakhelidze, S., Gabunia T., Sanikidze, T., 2022. Complex study of Cancer Morbidity and Inflammatory Markers, Presented in the Blood Serum of the Rural Population of Sachkhere District of Georgia. Asian Pac J Cancer Prev. 23, 6, 2127-2135. DOI: 10.31557/APJCP.2022.23.6.2127.
[5] Antunes, R.F., Brandão, C., Maia, M., Arosa, F.A., 2011. Red blood cells release factors with growth and survival bioactivities for normal and leukemic T cells. Immunology and cell biology 89, 111-121. DOI: 10.1038/icb.2010.60
[6] D’Alessandro, A., Zolla, L., 2017. Proteomic analysis of red blood cells and the potential for the clinic: what have we learned so far? Expert Rev Proteomics. 14, 3, 243-52. DOI: 10.1080/14789450.2017.1291347.
[7] Antunes, R.F., Brandao, C., Maia, M., Arosa, F.A., 2011. Red blood cells release factors with growth and survival bioactivities for normal and leukemic T cells. Immunol Cell Biol. 89, 1, 111-21. DOI: 10.1038/icb.2010.60.
[8] Groen, K., Maltby, V.E., Sanders, K.A., Scott, R.J. Tajouri, L., Lechner-Scott, J., 2016. Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology? Mult Scler J - Exp Transl Clin. 2:2055217316649981. DOI: 10.1177/2055217316649981.
[9] Varlet-Marie, E., Maso, F., Lac, G., , JF., 2004. Hemorheological disturbances in the overtraining syndrome. Clin Hemorheol Microcirc. 30, 3-4, 211-8. PMID: 15258345.
[10] Fornal, M., Lekki, J., Królczyk, J., Wizner, B., Grodzicki, T., 2021. Association of sulfur content in erythrocytes with cardiovascular parameters and blood pressure. Clin Hemorheol Microcirc. 79, 2, 279-292. DOI: 10.3233/CH-211117. PMID: 34057138.
[11] Olumuyiwa-Akeredolu, O.O., Soma, P., Buys, A.V., Debusho, L.K., Pretorius, E., 2017. Characterizing pathology in erythrocytes using morphological and biophysical membrane properties: Relation to impaired hemorheology and cardiovascular function in rheumatoid arthritis. Biochim Biophys Acta - Biomembr. 1859(12). DOI: 10.1016/j.bbamem.2017.09.014.
[12] Lee, S.B., Kim, Y.S., Kim J.H., Park, K., Nam, J.S., Kang, S., Park, J.S,, Shin, S., Ahn, C.W., 2019. Use of RBC deformability index as an early marker of diabetic nephropathy. Clin Hemorheol Microcirc. 72, 1, 75-84. DOI: 10.3233/CH-180434.PMID: 30452406.
[13] Lam, L.K.M., Murphy, S., Kokkinaki, D., Venosa, A., Sherrill-Mix, S., Casu, C., et al., 2019. DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci Transl Med. 13(616). DOI: 10.1126/scitranslmed.abj1008.
[14] Thomas, T., Stefanoni, D., Dzieciatkowska, M., Issaian, A., Nemkov, T., Hill, R.C., et al., 2021. Evidence of Structural Protein Damage and Membrane Lipid Remodeling in Red Blood Cells from COVID-19 Patients. J Proteome Res. 19, 11, 4455-4469. DOI: 10.1021/acs.jproteome.0c00606.
[15] Hernández-Hernández, A., Rodríguez, M.C., López-Revuelta, A., Sánchez-Gallego, J.I., Shnyrov, V., Llanillo, M., et al., 2006. Alterations in erythrocyte membrane protein composition in advanced non-small cell lung cancer. Blood Cells, Mol Dis. 36, 3,355-63. DOI: 10.1016/j.bcmd.2006.02.002.
[16] Kopczyński ,Z., Kuźniak, J., Thielemann, A., Kaczmarek, J., Rybczyńska, M., 1998. The biochemical modification of the erythrocyte membranes from women with ovarian cancer. Br J Cancer. 78, 4, 466-71. DOI: 10.1038/bjc.1998.516.
[17] Kaczmarek, J., Thieleman, A., Kopczyński, Z., Goslar, J., Hoffmann, S.K., Rybczyńska, M., 2002. Alterations in skeletal protein, distribution of PKCα, and level of phospholipids in erythrocyte membranes of women with primary breast cancer. Blood cells, Mol Dis. 29, 2, 225-35.
[18] Helwa, R., Heller, A., Knappskog, S., Bauer, A.S., 2017. Cells interact with red blood cells via galectin-4 - a short report. Cell Oncol. 40, 4,401-409. DOI: 10.1006/bcmd.2002.0562.
[19] Pribush, A., Hatskelzon, L., Mazor, D., Katorza, E., Zilberman-Kravits, D., Meyerstein, N., 2006. The role of erythrocyte aggregation in the abnormal hemorheology of multiple myeloma patients. Clin Hemorheol Microcirc. 34, 4,529-36. PMID: 16687792.
[20] Kvarackhelia, G., Kverenchkhiladze, R., Buleishvili, M., Sharashenidze, G., Sanikidze, T., Ormotsadze, G., 2017. Screening level environmental health risk assessment by health data in small areas of upper Imereti (Chiatura district). Georgian Med News. 270, 145-152. PMID: 28972501.
[21] Kvaratskhelia G, Tikaradze E, Buleishvili M, Sharashenidze G, Ormotsadze G, Sanikidze Т., 2018. The structure and risk of chronic morbidity in some villages of the upper Imereti region of West Georgia and their molecular and cytogenetic markers. Georgian Med News. 2018. 283, 97-103. PMID: 30516502.
[22] Sharashenidze, G., Tsimakuridze, M., Chkhikvishvili, I., Gabunia, T., Gogia, N., Ormotsadze, G., 2021. Bayesian modelling and inference of mixtures of distribution of blood total antiradical activity. Georgian Med News. 315,125-128. PMID: 34365438.
[23] Tikaradze E, Bakradze L, Tsimakuridze M, Zedgenidze A, Sanikidze T, Lomadze E, Ormotsadze G., 2021. Bayesian modelling and inference of mixtures of distribution of micronuclear buccal cells in the population of Sachkhere district’s villages. Georgian Med News. 316-317, 154-158. PMID: 34511463.
[24] Hasts, I., Olivia, I., 1989. Effect on the erythrocytes of the Ca2+/Mg2+-ATP-ase activity. J. Molecular and Cellular Biochemistry, 1, 87-93. DOI: 10.1007/BF00228283.
[25] Laemmli, V.K., 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. J. Nature, 227, 680-685.DOI: 10.1038/227680a0.
[26] Barbero, G., Carta, F., Giribaldi, G., Mandili, G., Crobu, S., Ceruti, C., Fontana, D., Destefanis, P., Turrini, F., 2006. Protein/RNA coextraction and small two-dimensional polyacrylamide gel electrophoresis for proteomic/gene expression analysis of renal cancer biopsies. Anal. Biochem. 349, 62-71. DOI: 10.1016/j.ab.2005.10.020.
[27] Sender, R., Fuchs, S., Milo, R., 2016. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 14, 8, e1002533. DOI: 10.1371/journal.pbio.1002533.
[28] Hu, L., Li, M., Ding, Y., Pu, L, Liu, J., Xie, J., Cabanero, M., Li, J., Xiang, R., Xiong, S., 2017. Prognostic value of RDW in cancers: a systematic review and meta-analysis. Oncotarget. 28, 8, 9, 16027-16035. DOI: 10.18632/oncotarget.13784.
[29] Li, Y., Xing, C., Wu, H., Hu, X., Li, S., Sun, G., Zhang, G., Wu, B, Zhang, F., Li , Z., 2019. Combining Red Blood Cell Distribution Width (RDW-CV) and CEA Predict Poor Prognosis for Survival Outcomes in Colorectal Cancer. J Cancer. 10, 5,1162–70. DOI: 10.7150/jca.29018.
[30] Zhou, Y., Li, X., Lu, Z., Zhang, L., Dai, T., 2020. Prognostic significance of red blood cell distribution width in gastrointestinal cancers: A meta-analysis. Medicine (Baltimore). 99, 16, e19588. DOI: 10.1097/MD.0000000000019588.
[31] Todua F, Ormotsadze G, Nadareishvili D, Sanikidze T, Mardaleishvili K., 2013. Functional state of red blood system as a possible predictor of individual radiosensitivity and carcinogenesis. Georgian Med News. 222,13-7. PMID: 24099809.
[32] Montagnana, M., Danese, E., 2016. Red cell distribution width and cancer. Ann Transl Med. 4,20,399. PMC5107391.
[33] Aoki, T.A., 2017. Comprehensive Review of Our Current Understanding of Red Blood Cell (RBC) Glycoproteins. Membranes (Basel), 7, 4,56. DOI: 10.3390/membranes7040056.
[34] Chasis, J.A., Mohandas, N., 1992. Red Blood Cell Glycophorins. Blood. 80,8,1869-1879. PMID: 1391951.
[35] Telen, M.J., 2005. Erythrocyte adhesion receptors: blood group antigens and related molecules, nsfusion Medicine Reviews. 19, 1, 32-44. DOI: 10.1016/j.tmrv.2004.09.006.
[36] Said AS, Rogers SC, Doctor A., 2018. Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions. Front Physiol. 12, 8, 1120. DOI: 10.3389/fphys.2017.01120.
[37] Wen, Z., Yao, W., Xie, L., Yan, Z.Y., Chen, K., Ka, W., Sun, D., 2000. Influence of neuraminidase on the characteristics of microrheology of red blood cells. Clin Hemorheol Microcirc. 23, 1, 51-7. PMID: 11214713.
[38] Williamson, R.C., Toye, A.M., 2008. Glycophorin A: Band 3 aid. Blood Cells Mol Dis. 41, 1, 35-43. DOI: 10.1016/j.bcmd.2008.01.001.
[39] Auffray, I., Marfatia, Sh., de Jong, K., Lee, G., Huang, Ch-H,, Paszty, Ch., Tanner, M.A., Mohandas, N., Chasis, J.N., 2001. Glycophorin A dimerization and band 3 interaction during erythroid membrane biogenesis: in vivo studies in human glycophorin A transgenic mice. BLOOD, 97, 9, 2872-2878. DOI: 10.1182/blood.v97.9.2872.
[40] Brosig, B., Langosch, D., 1998. The dimerization motif of the glycophorin A transmembrane segment in membranes Importance of glycine residues:. The GxxxG element thus appears to be the most crucial part of the interaction motif. Protein Science. 7, 4, 71052-1056. DOI: 10.1002/pro.5560070423.
[41] Rauk, S., Armstrong, DA., 2000. Influence of β-Sheet Structure on the Susceptibility of Proteins to Backbone Oxidative Damage: Preference for αC-Centered Radical Formation at Glycine Residues of Antiparallel β-Sheets. J. Am. Chem. Soc. 122,17, 4185-4192. DOI:10.1021/ja9939688.
[42] Liu, P.F., Avramova, L.V., Park, C., 2009. Revisiting absorbance at 230 nm as a protein unfolding probe. Analytical Biochemistry.389, 2, 165-70. DOI: 10.1016/j.ab.2009.03.028.
[43] Marinko, J.T., Huang, H., Penn, W.D., Capra, J.A., Schlebach J.P., Sanders. C.R., 2019. Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis. Chem Rev, 119,5537-5606. DOI: 10.1021/acs.chemrev.8b00532.
[44] Winterbourn, CC, Kettle, A.J., 2012. Redox reactions and microbial killing in the neutrophil phagosome. Antioxid Redox Signal. 18, 642–660.DOI: 10.1089/ars.2012.4827.
[45] Medicherla, B, Goldberg, A.L., 2008. Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins. J Cell Biol. 2008; 33, 182, 663-673. DOI: 10.1083/jcb.200803022
[46] Reichmann D., Voth, W., and Jakob, U., 2018. Maintaining a Healthy Proteome during Oxidative Stress Mol Cell. 18; 69, 2, 203-213. DOI: 10.1016/j.molcel.2017.12.021
[47] Antonova, N., 2012. On Some Mathematical Models in Hemorheology, Biotechnology & Biotechnological Equipment, 26, 5, 3286-3291, DOI: 10.5504/BBEQ.2012.0069
[48] Khoory, J., Estanislau, J., Elkhal, A., Lazaar, A., Melhorn, M.I,, Brodsky, A., Illigens, B., Hamachi, I, Kurishita, Y, Ivanov, A.R., Shevkoplyas, S., Shapiro, N.I, Ghiran, I,C., 2016. Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function. PLoS ONE.11,1,e0141206. DOI: 10.1371/journal.pone.0141206.
[49] O'Brien, R.W,, Beattie, J.K., Djerdjev, A,M., 2014. The electrophoretic mobility of an uncharged particle. J Colloid Interface Sci. 15; 420, 70-3. DOI: 10.1016/j.jcis.2013.10.047. PMID: 24559702.
[50] Beloborodov, S, S., Krylova, S.M., Krylov, S.N., 2019. Spherical-Shape Assumption for Protein-Aptamer Complexes Facilitates Prediction of Their Electrophoretic Mobility. Anal Chem. 15; 91, 20, 12680-12687. DOI: 10.1021/acs.analchem.9b02019.
[51] Hellman, L.M., Fried, M.G., 2007. Electrophoretic mobility shift assay (EMSA) for detecting protein-nucleic acid interactions. Nat Protoc. 2, 8, 1849-61. DOI: 10.1038/nprot.2007.249. PMID: 17703195; PMCID: PMC2757439.
[52] Antonova, N.,2012. Methods in blood rheology -from theoretical and experimental approach to clinical applications, J. Series on Biomechanics. 27, 1-2, 44-50, Marin Drinov Publ. House, Sofia (ISSN: 1313-2458).
|
|
| Date published: 2023-08-02
Download full text (Price of one pdf file: 39.00 BGN/20.00 EUR)
