Skip to main content
SpringerLink
Log in

In vitro human serum albumin glycation monitored by Terahertz spectroscopy

  • Published:
Optical and Quantum Electronics Aims and scope Submit manuscript

Abstract

The nonenzymatic attachment of sugars to proteins, namely glycation, is accelerated under diabetic conditions. Monitoring the glycated human serum albumin (HSA) levels gives the short term variation of glucose concentration in diabetic patients blood. Therefore, a significant effort was made to measure glycated HSA, including by spectroscopic methods such as Raman. Here we used THz spectroscopy to monitor HSA glycation in time (over 5, 7 and 11 weeks). Different sugar types have different reactivity; therefore we also addressed the reducing sugar influence on glycation by performing in vitro HSA glycation by both glucose and fructose. Since residues protonation state influences their susceptibility for glycation, we incubated HSA with sugars at two pH values: 7 and 8. Our results show that THz absorption decreases with the incubation time of HSA with sugars. At the incubation times we considered, the most significant differences were obtained on HSA samples glycated using glucose. Differences between samples glycated by glucose and by fructose show that glycation by glucose is a slower process. At pH 7, glycation by glucose is slower than at pH 8, while glycation by fructose is slightly faster at pH 7 than at pH 8. Glycated HSA models with different degrees of glycation were built by molecular modeling. Simulated THz spectra of the models are in good agreement with the experimental data. All these show that THz spectroscopy could monitor the progression of glycation in time and that it is sensitive to reducing sugars or pH value used in the glycation process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahmed, N., Thornalley, P.J.: Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and intrinsic fluorescence. Biochem. J. 364(Pt 1), 15–24 (2002)

    Google Scholar 

  • Balu, R., Zhang, H., Zukowski, E., Chen, J.Y., Markelz, A.G., Gregurick, S.K.: Terahertz spectroscopy of bacteriorhodopsin and rhodopsin: similarities and differences. Biophys. J. 94(8), 3217–3226 (2008)

    Article  ADS  Google Scholar 

  • Barnaby, O.S.: Characterization of Glycation Sites on Human Serum Albumin using Mass Spectrometry. University of Nebraska, Lincoln (2010)

    Google Scholar 

  • Barnaby, O.S., Wa, C., Cerny, R.L., Clarke, W., Hage, D.S.: Quantitative analysis of glycation sites on human serum albumin using (16)O/(18)O-labeling and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Clin. Chim. Acta 411(15–16), 1102–1110 (2010)

    Article  Google Scholar 

  • Barnaby, O.S., Cerny, R.L., Clarke, W., Hage, D.S.: Quantitative analysis of glycation patterns in human serum albumin using 16O/18O-labeling and MALDI-TOF MS. Clin. Chim. Acta 412(17–18), 1606–1615 (2011a)

    Article  Google Scholar 

  • Barnaby, O.S., Cerny, R.L., Clarke, W., Hage, D.S.: Comparison of modification sites formed on human serum albumin at various stages of glycation. Clin. Chim. Acta 412(3–4), 277–285 (2011b)

    Article  Google Scholar 

  • Best, R.B., Zhu, X., Shim, J., Lopes, P.E., Mittal, J., Feig, M., Mackerell Jr, A.D.: Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone phi, psi and side-chain chi(1) and chi(2) dihedral angles. J. Chem. Theory. Comput. 8(9), 3257–3273 (2012)

    Article  Google Scholar 

  • Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., K, M.: CHARMM: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations. J. Comp. Chem. 4(2), 187–217 (1983)

    Article  Google Scholar 

  • Bry, L., Chen, P.C., Sacks, D.B.: Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin. Chem. 47(2), 153–163 (2001)

    Google Scholar 

  • Chesne, S., Rondeau, P., Armenta, S., Bourdon, E.: Effects of oxidative modifications induced by the glycation of bovine serum albumin on its structure and on cultured adipose cells. Biochimie 88(10), 1467–1477 (2006)

    Article  Google Scholar 

  • Chiou, Y.J., Tomer, K.B., Smith, P.C.: Effect of nonenzymatic glycation of albumin and superoxide dismutase by glucuronic acid and suprofen acyl glucuronide on their functions in vitro. Chem. Biol. Interact. 121(2), 141–159 (1999)

    Article  Google Scholar 

  • Curry, S.: Lessons from the crystallographic analysis of small molecule binding to human serum albumin. Drug. Metab. Pharmacokinet. 24(4), 342–357 (2009)

    Article  Google Scholar 

  • Dingari, N.C., Horowitz, G.L., Kang, J.W., Dasari, R.R., Barman, I.: Raman spectroscopy provides a powerful diagnostic tool for accurate determination of albumin glycation. PLoS ONE 7(2), e32406 (2012)

    Article  ADS  Google Scholar 

  • Gabbay, K.H., Kinoshita, J.H.: Mechanism of development and possible prevention of sugar cataracts. Isr. J. Med. Sci. 8(8), 1557–1561 (1972)

    Google Scholar 

  • George, D.K., Knab, J.R., Yunfen, H., Kumauchi, M., Birge, R.R., Hoff, W.D., Markelz, A.G.: Photoactive Yellow Protein Terahertz Response: Hydration, Heating and Intermediate States. IEEE Transactions on Terahertz Science and Technology 3(3), 288–294 (2013)

    Article  ADS  Google Scholar 

  • Hao, J., Kitts, D., Pandalai, S.: Physiological and pharmacological properties of maillard reaction products. In: Pandalai, S.G. (eds.) Recent Research Developments in Molecular & Cellular Biochemistry, Vol. 1, pp. 59–75 (2003)

  • Harrick, N.J.: Internal Reflection Spectroscopy. Harrick Scientific Corp, New York (1987)

    Google Scholar 

  • He, Y., Chen, J.Y., Knab, J.R., Zheng, W., Markelz, A.G.: Evidence of protein collective motions on the picosecond timescale. Biophys.l J. 100(4), 1058–1065 (2011)

    Article  ADS  Google Scholar 

  • Heaf, D.J., Galton, D.J.: Sorbitol and other polyols in lens, adipose tissue and urine in diabetes mellitus. Clin. Chim. Acta 63(1), 41–47 (1975)

    Article  Google Scholar 

  • Hom, F.G., Ettinger, B., Lin, M.J.: Comparison of serum fructosamine vs glycohemoglobin as measures of glycemic control in a large diabetic population. Acta Diabetol. 35(1), 48–51 (1998)

    Article  Google Scholar 

  • Iberg, N., Fluckiger, R.: Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites. J. Biol. Chem. 261(29), 13542–13545 (1986)

    Google Scholar 

  • Kitabchi, A.E., Umpierrez, G.E., Miles, J.M., Fisher, J.N.: Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32(7), 1335–1343 (2009)

    Article  Google Scholar 

  • Ko, G.T., Chan, J.C., Yeung, V.T., Chow, C.C., Tsang, L.W., Li, J.K., So, W.Y., Wai, H.P., Cockram, C.S.: Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects. Diabetes Care 21(8), 1221–1225 (1998)

    Article  Google Scholar 

  • Koyama, H., Sugioka, N., Uno, A., Mori, S., Nakajima, K.: Effects of glycosylation of hypoglycaemic drug binding to serum albumin. Biopharm. Drug Dispos. 18(9), 791–801 (1997)

    Article  Google Scholar 

  • Kumeda, Y., Inaba, M., Shoji, S., Ishimura, E., Inariba, H., Yabe, S., Okamura, M., Nishizawa, Y.: Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes. Clin. Endocrinol. (Oxf) 69(4), 556–561 (2008)

    Article  Google Scholar 

  • Lalla, E., Lamster, I.B., Drury, S., Fu, C., Schmidt, A.M.: Hyperglycemia, glycoxidation and receptor for advanced glycation endproducts: potential mechanisms underlying diabetic complications, including diabetes-associated periodontitis. Periodontol. 2000(23), 50–62 (2000)

    Article  Google Scholar 

  • Lapolla, A., Fedele, D., Reitano, R., Bonfante, L., Guizzo, M., Seraglia, R., Tubaro, M., Traldi, P.: Mass spectrometric study of in vivo production of advanced glycation end-products/peptides. J. Mass. Spectrom. 40(7), 969–972 (2005)

    Article  Google Scholar 

  • Li, H., Robertson, A.D., Jensen, J.H.: Very fast empirical prediction and rationalization of protein pKa values. Proteins 61(4), 704–721 (2005)

    Article  Google Scholar 

  • Macdonald, I., Keyser, A., Pacy, D.: Some effects, in man, of varying the load of glucose, sucrose, fructose, or sorbitol on various metabolites in blood. Am. J. Clin. Nutr. 31(8), 1305–1311 (1978)

    Google Scholar 

  • MacKerell, A.D., Bashford, D., Bellott, M., Dunbrack, R.L., Evanseck, J.D., Field, M.J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F.T.K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D.T., Prodhom, B., Reiher, W.E., Roux, B., Schlenkrich, M., Smith, J.C., Stote, R., Straub, J., Watanabe, M., Wiorkiewicz-Kuczera, J., Yin, D., Karplus, M.: All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102(18), 3586–3616 (1998)

    Article  Google Scholar 

  • MacKerell Jr, A.D., Feig, M., Brooks 3rd, C.L.: Improved treatment of the protein backbone in empirical force fields. J. Am. Chem. Soc. 126(3), 698–699 (2004)

    Article  Google Scholar 

  • Makita, Z., Vlassara, H., Cerami, A., Bucala, R.: Immunochemical detection of advanced glycosylation end products in vivo. J. Biol. Chem. 267(8), 5133–5138 (1992)

    Google Scholar 

  • Markelz, A., Whitmire, S., Hillebrecht, J., Birge, R.: THz time domain spectroscopy of biomolecular conformational modes. Phys. Med. Biol. 47(21), 3797–3805 (2002)

    Article  Google Scholar 

  • Mernea, M., Calborean, O., Grigore, O., Dascalu, T., Mihailescu, D.F.: Validation of protein structural models using THz spectroscopy: a promising approach to solve three-dimensional structures. Opt. Quant. Electron. 46(4), 505–514 (2014)

    Article  Google Scholar 

  • Nakajou, K., Watanabe, H., Kragh-Hansen, U., Maruyama, T., Otagiri, M.: The effect of glycation on the structure, function and biological fate of human serum albumin as revealed by recombinant mutants. Biochim. Biophys. Acta. 1623(2–3), 88–97 (2003)

    Article  Google Scholar 

  • Neglia, C.I., Cohen, H.J., Garber, A.R., Ellis, P.D., Thorpe, S.R., Baynes, J.W.: 13C NMR investigation of nonenzymatic glucosylation of protein. Model studies using RNase A. J. Biol. Chem. 258(23), 14279–14283 (1983)

    Google Scholar 

  • Negre-Salvayre, A., Salvayre, R., Auge, N., Pamplona, R., Portero-Otin, M.: Hyperglycemia and glycation in diabetic complications. Antioxid. Redox. Signal 11(12), 3071–3109 (2009)

    Article  Google Scholar 

  • Okumura, A., Mitamura, Y., Namekata, K., Nakamura, K., Harada, C., Harada, T.: Glycated albumin induces activation of activator protein-1 in retinal glial cells. Jpn. J. Ophthalmol. 51(3), 236–237 (2007)

    Article  Google Scholar 

  • Perejda, A.J., Uitto, J.: Nonenzymatic glycosylation of collagen and other proteins: relationship to development of diabetic complications. Coll. Relat. Res. 2(1), 81–88 (1982)

    Article  Google Scholar 

  • Phillips, J.C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R.D., Kale, L., Schulten, K.: Scalable molecular dynamics with NAMD. J. Comput. Chem. 26(16), 1781–1802 (2005)

    Article  Google Scholar 

  • Roche, M., Rondeau, P., Singh, N.R., Tarnus, E., Bourdon, E.: The antioxidant properties of serum albumin. FEBS Lett. 582(13), 1783–1787 (2008)

    Article  Google Scholar 

  • Rogozinski, S., Blumenfeld, O.O., Seifter, S.: The nonenzymatic glycosylation of collagen. Arch. Biochem. Biophys. 221(2), 428–437 (1983)

    Article  Google Scholar 

  • Rondeau, P., Navarra, G., Cacciabaudo, F., Leone, M., Bourdon, E., Militello, V.: Thermal aggregation of glycated bovine serum albumin. Biochim. Biophys. Acta 1804(4), 789–798 (2010)

    Article  Google Scholar 

  • Rondeau, P., Bourdon, E.: The glycation of albumin: structural and functional impacts. Biochimie 93(4), 645–658 (2011)

    Article  Google Scholar 

  • Roohk, H.V., Zaidi, A.R.: A review of glycated albumin as an intermediate glycation index for controlling diabetes. J. Diabetes Sci. Technol. 2(6), 1114–1121 (2008)

    Article  Google Scholar 

  • Suarez, G., Rajaram, R., Oronsky, A.L., Gawinowicz, M.A.: Nonenzymatic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose. J. Biol. Chem. 264(7), 3674–3679 (1989)

    Google Scholar 

  • Sugio, S., Kashima, A., Mochizuki, S., Noda, M., Kobayashi, K.: Crystal structure of human serum albumin at 2.5 A resolution. Protein. Eng. 12(6), 439–446 (1999)

    Article  Google Scholar 

  • Tama, F., Gadea, F.X., Marques, O., Sanejouand, Y.H.: Building-block approach for determining low-frequency normal modes of macromolecules. Proteins 41(1), 1–7 (2000)

    Article  Google Scholar 

  • Wa, C., Cerny, R.L., Clarke, W.A., Hage, D.S.: Characterization of glycation adducts on human serum albumin by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Clin. Chim. Acta 385(1–2), 48–60 (2007)

    Article  Google Scholar 

  • Watala, C.: Role of nonenzymatic glycosylation of proteins in disorders of erythrocytes and blood platelets in diabetes mellitus. Acta Haematol. Pol. 24(2), 95–101 (1993)

    Google Scholar 

  • Zhang, Q., Ames, J.M., Smith, R.D., Baynes, J.W., Metz, T.O.: A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J. Proteome. Res. 8(2), 754–769 (2009)

    Article  Google Scholar 

  • Zheng, C.M., Ma, W.Y., Wu, C.C., Lu, K.C.: Glycated albumin in diabetic patients with chronic kidney disease. Clin. Chim. Acta 413(19–20), 1555–1561 (2012)

    Article  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the financial support of the Romanian Ministry of Education, Research, Youth and Sport through the “IDEAS” Project 137/2011 and the “PCCA” Project 89/2012. The authors thank COST Action MP1204 for supporting the attendance of Prof. Dan Mihailescu to the Second Annual Conference of COST Action MP1204 and SMMO2014.

Author information

Authors and Affiliations

  1. Faculty of Biology, University of Bucharest, Splaiul Independentei, No 91-95, 050095, Bucharest, Romania

    Maria Mernea, Alina Ionescu, Cristina Nica, Gheorghe Stoian & Dan Florin Mihailescu

  2. Laboratory of Solid-State Quantum Electronics, National Institute for Laser, Plasma and Radiation Physics, PO Box MG-36, 077125, Magurele, Romania

    Alina Ionescu & Traian Dascalu

  3. Doctoral School of Physics, University of Bucharest, Atomistilor Street, No 405, 077125, Magurele, Romania

    Ionut Vasile

  4. Horia Hulubei National Institute for Physics and Nuclear Engineering, PO Box MG-6, 077125, Magurele, Romania

    Ionut Vasile

Authors
  1. Maria Mernea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alina Ionescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ionut Vasile
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina Nica
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gheorghe Stoian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Traian Dascalu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dan Florin Mihailescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ionut Vasile.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mernea, M., Ionescu, A., Vasile, I. et al. In vitro human serum albumin glycation monitored by Terahertz spectroscopy. Opt Quant Electron 47, 961–973 (2015). https://doi.org/10.1007/s11082-015-0129-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11082-015-0129-y

Keywords

Search

Navigation