Biopolym. Cell. 1999; 15(3):200-206.
Structural and functional modification of the regulatory tropomyosin-troponin protein complex of cardiac myofllaments during heart diseases development
1Fedorkova O. M., 1Sidorik L. L.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


The review summaries literature and authors data about the role of tropomyosin and troponin complex from cardiac myofilaments during heart diseases development. The role of tropomyosin and troponins in dilated cardiomyopathy pathogenesis was discussed.


[1] Farah CS, Reinach FC. The troponin complex and regulation of muscle contraction. FASEB J. 1995;9(9):755-67.
[2] Ivanov II, Korovkin BF, Pinayev GP. Muscular contraction. M.: Medicine, 1977. 344.
[3] Farah CS, Miyamoto CA, Ramos CH, da Silva AC, Quaggio RB, Fujimori K, Smillie LB, Reinach FC. Structural and regulatory functions of the NH2- and COOH-terminal regions of skeletal muscle troponin I. J Biol Chem. 1994;269(7):5230-40.
[4] Rethinasamy P, Muthuchamy M, Hewett T, Boivin G, Wolska BM, Evans C, Solaro RJ, Wieczorek DF. Molecular and physiological effects of alpha-tropomyosin ablation in the mouse. Circ Res. 1998;82(1):116-23.
[5] Betteridge DR, Lehrer SS. Two conformational states of didansylcystine-labeled rabbit cardiac tropomyosin. J Mol Biol. 1983;167(2):481-96.
[6] Muthuchamy M, Pajak L, Howles P, Doetschman T, Wieczorek DF. Developmental analysis of tropomyosin gene expression in embryonic stem cells and mouse embryos. Mol Cell Biol. 1993;13(6):3311-23.
[7] Ebashi S, Kodama A. A new protein factor promoting aggregation of tropomyosin. J Biochem. 1965;58(1):107-8.
[8] Greaser ML, Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem. 1971;246(13):4226-33.
[9] Greaser ML, Gergely J. Purification and properties of the components from tropinin. J Biol Chem. 1973;248(6):2125-33.
[10] Permyakov EA. parvalbumin: and related calcium-binding proteins. M.: Nauka, 1985. 192.
[11] Potter JD, Gergely J. The calcium and magnesium binding sites on troponin and their role in the regulation of myofibrillar adenosine triphosphatase. J Biol Chem. 1975;250(12):4628-33.
[12] Satyshur KA, Rao ST, Pyzalska D, Drendel W, Greaser M, Sundaralingam M. Refined structure of chicken skeletal muscle troponin C in the two-calcium state at 2-A resolution. J Biol Chem. 1988;263(4):1628-47.
[13] Johnson JD, Potter JD. Detection of two classes of Ca2+ binding sites in troponin C with circular dichroism and tyrosine fluorescence. J Biol Chem. 1978;253(11):3775-7.
[14] Potter JD, Jonson JD, Mamlel F. Calcium binding poteins: relationship of binding, structure, conformation and biological functions. I Calcium binding proteins and calcium function. New York: North-Holland, 1977:239—250.
[15] Malnic B, Reinach FC. Assembly of functional skeletal muscle troponin complex in Escherichia coli. Eur J Biochem. 1994;222(1):49-54.
[16] Talbot JA, Hodges RS. Synthetic studies on the inhibitory region of rabbit skeletal troponin I. Relationship of amino acid sequence to biological activity. J Biol Chem. 1981;256(6):2798-802.
[17] Murphy AM, Jones L 2nd, Sims HF, Strauss AW. Molecular cloning of rat cardiac troponin I and analysis of troponin I isoform expression in developing rat heart. Biochemistry. 1991;30(3):707-12.
[18] Zhang R, Zhao J, Mandveno A, Potter JD. Cardiac troponin I phosphorylation increases the rate of cardiac muscle relaxation. Circ Res. 1995;76(6):1028-35.
[19] Johnson JD, Charlton SC, Potter JD. A fluorescence stopped flow analysis of Ca2+ exchange with troponin C. J Biol Chem. 1979;254(9):3497-502.
[20] Robertson SP, Johnson JD, Potter JD. The time-course of Ca2+ exchange with calmodulin, troponin, parvalbumin, and myosin in response to transient increases in Ca2+. Biophys J. 1981;34(3):559-69.
[21] Johnson JD, Nakkula RJ, Vasulka C, Smillie LB. Modulation of Ca2+ exchange with the Ca(2+)-specific regulatory sites of troponin C. J Biol Chem. 1994;269(12):8919-23.
[22] Mesnard L, Logeart D, Taviaux S, Diriong S, Mercadier JJ, Samson F. Human cardiac troponin T: cloning and expression of new isoforms in the normal and failing heart. Circ Res. 1995;76(4):687-92.
[23] Greig A, Hirschberg Y, Anderson PA, Hainsworth C, Malouf NN, Oakeley AE, Kay BK. Molecular basis of cardiac troponin T isoform heterogeneity in rabbit heart. Circ Res. 1994;74(1):41-7.
[24] Hunkeler NM, Kullman J, Murphy AM. Troponin I isoform expression in human heart. Circ Res. 1991;69(5):1409-14.
[25] Gulati J, Scordilis S, Babu A. Effect of troponin C on the cooperativity in Ca2+ activation of cardiac muscle. FEBS Lett. 1988;236(2):441-4.
[26] Blanchard EM, Iizuka K, Christe M, Conner DA, Geisterfer-Lowrance A, Schoen FJ, Maughan DW, Seidman CE, Seidman JG. Targeted ablation of the murine alpha-tropomyosin gene. Circ Res. 1997;81(6):1005-10.
[27] MacLeod AR, Gooding C. Human hTM alpha gene: expression in muscle and nonmuscle tissue. Mol Cell Biol. 1988;8(1):433-40.
[28] Saba Z, Nassar R, Ungerleider RM, Oakeley AE, Anderson PA. Cardiac troponin T isoform expression correlates with pathophysiological descriptors in patients who underwent corrective surgery for congenital heart disease. Circulation. 1996;94(3):472-6.
[29] Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group. Circulation. 1996;93(9):1651-7.
[30] Galvani M, Ottani F, Ferrini D, Ladenson JH, Destro A, Baccos D, Rusticali F, Jaffe AS. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation. 1997;95(8):2053-9.
[31] Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, Fischer GA, Fung AY, Thompson C, Wybenga D, Braunwald E. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996;335(18):1342-9.
[32] Jin JP, Huang QQ, Yeh HI, Lin JJ. Complete nucleotide sequence and structural organization of rat cardiac troponin T gene. A single gene generates embryonic and adult isoforms via developmentally regulated alternative splicing. J Mol Biol. 1992;227(4):1269-76.
[33] Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994;77(5):701-12.
[34] Watkins H., McKenna W. J., Thietfelder L, Suk H. J, Aiuin R., Donoghue A., Spirito P., Matsumori A., Moravec C. S., Siedman J. G., Seidman C. Mutations in the genes for cardiac troponin T and -tropomyosin in hypertrophic cardiomyopathy. New Engl. J. Med. 1995. 332:1058—1063.
[35] Solomon SD, Wolff S, Watkins H, Ridker PM, Come P, McKenna WJ, Seidman CE, Lee RT. Left ventricular hypertrophy and morphology in familial hypertrophic cardiomyopathy associated with mutations of the beta-myosin heavy chain gene. J Am Coll Cardiol. 1993;22(2):498-505.
[36] Marian AJ, Zhao G, Seta Y, Roberts R, Yu QT. Expression of a mutant (Arg92Gln) human cardiac troponin T, known to cause hypertrophic cardiomyopathy, impairs adult cardiac myocyte contractility. Circ Res. 1997;81(1):76-85.
[37] Forissier JF, Carrier L, Farza H, Bonne G, Bercovici J, Richard P, Hainque B, Townsend PJ, Yacoub MH, Fauri S, Dubourg O, Millaire A, Haguge AA, Desnos M, Komajda M, Schwartz K. Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy. Circulation. 1996;94(12):3069-73.
[38] Yamauchi-Takihara K, Nakajima-Taniguchi C, Matsui H, Fujio Y, Kunisada K, Nagata S, Kishimoto T. Clinical implications of hypertrophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene. Heart. 1996;76(1):63-5.
[39] Gulati J, Akella AB, Nikolic SD, Starc V, Siri F. Shifts in contractile regulatory protein subunits troponin T and troponin I in cardiac hypertrophy. Biochem Biophys Res Commun. 1994;202(1):384-90.
[40] Alonsozana GL, Christenson RH. The case for cardiac troponin T: marker for effective risk stratification of patients with acute cardiac ischemia. Clin Chem. 1996;42(5):803-8.
[41] Brogan GX Jr, Friedman S, McCuskey C, Cooling DS, Berrutti L, Thode HC Jr, Bock JL. Evaluation of a new rapid quantitative immunoassay for serum myoglobin versus CK-MB for ruling out acute myocardial infarction in the emergency department. Ann Emerg Med. 1994;24(4):665-71.
[42] Gibler WB, Runyon JP, Levy RC, Sayre MR, Kacich R, Hattemer CR, Hamilton C, Gerlach JW, Walsh RA. A rapid diagnostic and treatment center for patients with chest pain in the emergency department. Ann Emerg Med. 1995;25(1):1-8.
[43] Lott JA, Stang JM. Differential diagnosis of patients with abnormal serum creatine kinase isoenzymes. Clin Lab Med. 1989;9(4):627-42.
[44] Apple FS. Acute myocardial infarction and coronary reperfusion. Serum cardiac markers for the 1990s. Am J Clin Pathol. 1992;97(2):217-26.
[45] Van de Werf F. Cardiac troponins in acute coronary syndromes. N Engl J Med. 1996;335(18):1388-9.
[46] Wu AH. Cardiac troponin T: biochemical, analytical and clinical aspects. J Clin Immunoassay. 1994. 17:45—48.
[47] Ohman EM, Armstrong PW, Christenson RH, Granger CB, Katus HA, Hamm CW, O'Hanesian MA, Wagner GS, Kleiman NS, Harrell FE Jr, Califf RM, Topol EJ. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators. N Engl J Med. 1996;335(18):1333-41.
[48] Katus HA, Remppis A, Looser S, Hallermeier K, Scheffold T, K?bler W. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol. 1989;21(12):1349-53.
[49] Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, Ottlinger ME. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation. 1997;96(8):2641-8.
[50] Zimmermann R, Baki S, Dengler TJ, Ring GH, Remppis A, Lange R, Hagl S, Kubler W, Katus HA. Troponin T release after heart transplantation. Br Heart J. 1993;69(5):395-8.
[51] Luscher MS1, Thygesen K, Ravkilde J, Heickendorff L. Applicability of cardiac troponin T and I for early risk stratification in unstable coronary artery disease. TRIM Study Group. Thrombin Inhibition in Myocardial ischemia. Circulation. 1997;96(8):2578-85.
[52] Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation. 1997;95(1):163-8
[53] Van Eyk JE, Powers F, Law W, Larue C, Hodges RS, Solaro RJ. Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa-force relation. Circ Res. 1998;82(2):261-71.
[54] Gao WD, Atar D, Liu Y, Perez NG, Murphy AM, Marban E. Role of troponin I proteolysis in the pathogenesis of stunned myocardium. Circ Res. 1997;80(3):393-9.
[55] Lofberg M, Tahtela R, Harkonen M, Somer H. Cardiac troponins in severe rhabdomyolysis. Clin Chem. 1996;42(7):1120-1.
[56] Li D, Keffer J, Corry K, Vazquez M, Jialal I. Nonspecific elevation of troponin T levels in patients with chronic renal failure. Clin Biochem. 1995;28(4):474-7.
[57] Siegel AJ, Sholar M, Yang J, Dhanak E, Lewandrowski KB. Elevated serum cardiac markers in asymptomatic marathon runners after competition: is the myocardium stunned? Cardiology. 1997;88(6):487-91.
[58] Durand JB, Bachinski LL, Bieling LC, Czernuszewicz GZ, Abchee AB, Yu QT, Tapscott T, Hill R, Ifegwu J, Marian AJ, et al. Localization of a gene responsible for familial dilated cardiomyopathy to chromosome 1q32. Circulation. 1995;92(12):3387-9.
[59] Limas CJ, Goldenberg IF, Limas C. Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy. Circ Res. 1989;64(1):97-103.
[60] Latif N, Baker CS, Dunn MJ, Rose ML, Brady P, Yacoub MH. Frequency and specificity of antiheart antibodies in patients with dilated cardiomyopathy detected using SDS-PAGE and western blotting. J Am Coll Cardiol. 1993;22(5):1378-84.
[61] Caforio AL, Goldman JH, Baig MK, Haven AJ, Dalla Libera L, Keeling PJ, McKenna WJ. Cardiac autoantibodies in dilated cardiomyopathy become undetectable with disease progression. Heart. 1997;77(1):62-7.
[62] Caforio AL, Grazzini M, Mann JM, Keeling PJ, Bottazzo GF, McKenna WJ, Schiaffino S. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation. 1992;85(5):1734-42.
[63] Sidorik LL, Rodnin NV, Bobyk VI, Ryabenko DV, Veberov AV, Tkachenko TYu, Matsuka GKh. Investigation of autoantibodies directed against tissue-specific myocardial antigens in dilated cardiomyopathy. Biopolym. Cell. 1995; 11(1):81-86
[64] Sidorik LL, Fedorkova OM, Kovenja TV, Bobyk VI, Rodnin NV, Matsuka GKh. Structural and functional studies of cardiac tropomyosin as; autoantigen at dilated cardiomyopathy. Biopolym. Cell. 1998; 14(3):203-209
[65] Khanna AK, Nomura Y, Fischetti VA, Zabriskie JB. Antibodies in the sera of acute rheumatic fever patients bind to human cardiac tropomyosin. J Autoimmun. 1997;10(1):99-106.
[66] Sargent SJ, Beachey EH, Corbett CE, Dale JB. Sequence of protective epitopes of streptococcal M proteins shared with cardiac sarcolemmal membranes. J Immunol. 1987;139(4):1285-90.
[67] Solaro RJ, Rarick HM. Troponin and tropomyosin: proteins that switch on and tune in the activity of cardiac myofilaments. Circ Res. 1998;83(5):471-80.
[68] Moiseyev VS Cardiomyopathy and myocarditis. Cardiology. 1996. 36. 74-85.
[69] Sato Y, Kataoka K, Matsumori A, Sasayama S, Yamada T, Ito H, Takatsu Y. Measuring serum aminoterminal type III procollagen peptide, 7S domain of type IV collagen, and cardiac troponin T in patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathy. Heart. 1997;78(5):505-8.
[70] Humphreys JE, Cummins P. Regulatory proteins of the myocardium. Atrial and ventricular tropomyosin and troponin-I in the developing and adult bovine and human heart. J Mol Cell Cardiol. 1984;16(7):643-57.
[71] Tobacman LS. Thin filament-mediated regulation of cardiac contraction. Annu Rev Physiol. 1996;58:447-81.
[72] Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996;93(5):841-2.