Analytical and Bioanalytical Chemistry

, Volume 398, Issue 3, pp 1395–1402 | Cite as

Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing

  • Henrik Andersson
  • Bertil Kågedal
  • Carl-Fredrik Mandenius
Original Paper

Abstract

Troponin T (TnT) is a useful biomarker for studying drug-induced toxicity effects on cardiac cells. We describe how a surface plasmon resonance (SPR) biosensor was applied to monitor the release of TnT from active HL-1 cardiomyocytes in vitro when exposed to cardiotoxic substances. Two monoclonal human TnT antibodies were compared in the SPR immunosensor to analyse the TnT release. The detection limit of TnT was determined to be 30 ng/ml in a direct assay set-up and to be 10 ng/ml in a sandwich assay format. Exposure of the cardiomyocytes to doxorubicin, troglitazone, quinidine and cobalt chloride for periods of 6 and 24 h gave significant SPR responses, whereas substances with low toxicity showed insignificant effects (ascorbic acid, methotrexate). The SPR results were verified with a validated immunochemiluminescence method which showed a correlation of r2 = 0.790.

Keywords

Surface plasmon resonance Troponin T Cardiotoxicity In vitro toxicity HL-1 cardiomyocytes Cytotoxicity screening 

Abbreviations

cTnT

cardiac troponin T

RU

resonance units

SPR

surface plasmon resonance

TnT

troponin T

References

  1. 1.
    Apple FS, Wu AH, Jaffe AS, Panteghini M, Christenson RH, Cannon CP, Jesse FG, DA RL M, Newby LK, Storrow AB, Tang WH, Pagani F, Tate J, Ordonez-Llanos J, Mair J (2007) Circulation 116:95–98CrossRefGoogle Scholar
  2. 2.
    Hessel MH, Michielsen EC, Atsma DE, Schalij MJ, van der Valk EJ, Bax WH, Hermens WT, van Dieijen-Visser MP, van der Laarse A (2008) Exp Mol Pathol 85:90–95CrossRefGoogle Scholar
  3. 3.
    Gaze DC, Collinson PO (2008) Ann Clin Biochem 45:349–355CrossRefGoogle Scholar
  4. 4.
    Alpert JS, Thygesen K, Antman E, Bassand JP (2000) J Am Coll Cardiol 36:959–969CrossRefGoogle Scholar
  5. 5.
    Wu AH, Feng YJ, Moore R, Apple FS, McPherson PH, Buechler KF, Bodor G (1998) Clin Chem 44:1198–1208Google Scholar
  6. 6.
    Michielsen EC, Diris JH, Kleijnen VW, Wodzig WK, Van Dieijen-Visser MP (2007) Clin Biochem 40:851–855CrossRefGoogle Scholar
  7. 7.
    Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME (1997) Circulation 96:2641–2648Google Scholar
  8. 8.
    Expert Workshop Group on Biomarkers of Drug-induced Cardiac Toxicity report to the Nonclinical Studies Subcommittee of the Advisory Committee for Pharmaceutical Science (2002) National Institute for Health and Clinical Excellence. http://www.nice.org.uk
  9. 9.
    Adamcová M, Sterba M, Simunek T, Potacová A, Popelová O, Mazurová O, Gersl V (2005) Expert Opin Drug Saf 4:457–469CrossRefGoogle Scholar
  10. 10.
    O’Brien PJ (2006) Expert Rev Mol Diagn 6:685–702CrossRefGoogle Scholar
  11. 11.
    O’Brien PJ (2008) Toxicology 245:206–218CrossRefGoogle Scholar
  12. 12.
    Stummann TC, Beilmann M, Duker G, Dumontier B, Fredriksson JM, Jones RL, Hasiwa M, Kang J, Mandenius CF, Mayer T, Minotti G, Valentin YJP, Zünckler BJ, Bremer S (2009) Cardiovasc Toxicol 9:107–125CrossRefGoogle Scholar
  13. 13.
    EU Council Directive 76/788/EEC of 27 July 1976 (Cosmetic Directive – redrafted 2008) http://ec.europa.eu/enterprise/sectors/cosmetics/documents/directive/index_en.htm
  14. 14.
    Marks RS et al (2007) In: Marks RS, Cullen DC, Karube I, Lowe CR, Weetall HH (eds) Handbook of biosensors and biochips. Hoboken, WileyGoogle Scholar
  15. 15.
    Spangler BD, Wilkinson EA, Murphy JT, Tyler BJ (2001) Anal Chim Acta 444:149–161CrossRefGoogle Scholar
  16. 16.
    Klein G, Kampmann M, Baum H, Rauscher T, Vukovic T, Hallermayer K, Rehner H, Muller-Bardorff M, Katus HA (1998) Wien Klin Wochenschr 110(Suppl 3):40–51Google Scholar
  17. 17.
    Wei J, Mu Y, Song D, Fang X, Liu X, Bu L, Zhang H, Zhang G, Ding J, Wang W, Jin Q, Luo G (2003) Anal Biochem 321:209–216CrossRefGoogle Scholar
  18. 18.
    Nedelkov D, Nelson RW (2006) Methods Mol Biol 328:131–139Google Scholar
  19. 19.
    Masson JF, Obando L, Beaudoin S, Booksh K (2004) Talanta 62:865–870CrossRefGoogle Scholar
  20. 20.
    Dutra RF, Kubota LT (2007) Clin Chim Acta 376:114–120CrossRefGoogle Scholar
  21. 21.
    Dutra RF, Mendes RK, Lins da Silva V, Kubota LT (2007) J Pharm Biomed Anal 43:1744–1750CrossRefGoogle Scholar
  22. 22.
    Tripet B, De Crescenzo G, Grothe S, O’Connor-McCount M, Hodge RS (2002) J Mol Biol 323:245–362CrossRefGoogle Scholar
  23. 23.
    Adamcová M, Simunek T, Kaiserová H, Popelová O, Sterba M, Potacová A, Vavrová J, Malaková J, Gersl V (2007) Toxicology 237:218–228CrossRefGoogle Scholar
  24. 24.
    Claycomb WC, Lanson NA, Stallworth BS, Egeland DB, Delcarpio JB, Bahinski A, Izzo NJ (1998) Proc Natl Acad Sci USA 95:2979–2984CrossRefGoogle Scholar
  25. 25.
    Safsten P, Klakamp SL, Drake AW, Karlsson R, Myszka DG (2006) Anal Biochem 353:181–190CrossRefGoogle Scholar
  26. 26.
    White SM, Constantin P, Claycomb WC (2004) Am J Physiol Heart Circ Physiol 286:H823–H829CrossRefGoogle Scholar
  27. 27.
    Ke L, Qi XY, Dijkhuis AJ, Chartier D, Nattel S, Henning RH, Kampinga HH, Brundel BJJM (2008) J Mol Cell Cardiol 45:685–693CrossRefGoogle Scholar
  28. 28.
    Lounes KC, Demeler B, Anderson DE, Gomes AW, Potter JD, Nassar R, Anderson PAW (2008) Biochemistry 47:1970–1976CrossRefGoogle Scholar
  29. 29.
    Giannitsis E, Kurz K, Hallermeyer K, Jarausch J, Jaffe AS, Katus HA (2010) Clin Chem 52:254–261CrossRefGoogle Scholar
  30. 30.
    Christenson RH, Duh SH, Apple FS, Bodor GS, Bunk DM, Panteghini M, Welch MJ, Wu AH, Kahn SE (2006) Clin Chem 52:1685–1692CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Henrik Andersson
    • 1
  • Bertil Kågedal
    • 2
  • Carl-Fredrik Mandenius
    • 1
  1. 1.Division of Biotechnology/IFMLinköping UniversityLinköpingSweden
  2. 2.Division of Clinical Chemistry, Department of Clinical and Experimental MedicineLinköping UniversityLinköpingSweden

Personalised recommendations