Developing the next generation of cardiac markers: Disease-induced modifications of troponin I

McDonough, Jason L.; Van Eyk, Jennifer E.

doi:10.1016/j.pcad.2004.07.001

Cited by 62Acute Myocardial Infarction ResearchCardiomyopathy and Myosin StudiesBiomarkers in Disease Mechanisms

Developing the next generation of cardiac markers: Disease-induced modifications of troponin I

McDonough, Jason L., Van Eyk, Jennifer E.·2004·Progress in Cardiovascular Diseases

DOI 10.1016/j.pcad.2004.07.001

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Abstract

Troponin I (TnI) and Troponin T (TnT) have evolved into arguably the two most important diagnostic markers for acute myocardial injury. Part of their diagnostic utility lies in the uniquely important roles that both TnI and TnT play in the calcium-dependent regulation of cardiac muscle contraction. Both proteins undergo extensive physiologic regulation, principally through phosphorylation, as well as specific disease-induced pathologic modifications, including phosphorylation, oxidation, and proteolysis. Many, if not all, of these protein modifications in some way modulate contractility, and when detected in serum may therefore provide important information about both the disease state and functional status of the heart. However, the complexity of the TnI (and TnT) forms in the serum is large, which leads to difficulty in detecting all of the Tn subunits in serum, and hence interpreting the biologic significance of each modified product. But, as diagnostic tools and modalities improve, our ability to monitor and detect specific disease-induced modified forms of proteins will inevitably lead to better and more specific diagnoses and therapies.

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The PTM profiles of cTnI can function as molecular fingerprints of cellular signaling pathway activity with the potential to serve as next-generation biomarkers.
“The PTM profiles of cTnI can function as molecular fingerprints of cellular signaling pathway activity with the potential to serve as the next-generation biomarkers27,32,33.”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [33]

Regulation of Contraction in Striated Muscle
Gordon, A. M., Homsher, E. E., & Regnier, M. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.2.853 · Cited by 1,740 · see citing works
Phosphorylation of troponin I and the inotropic effect of adrenaline in the perfused rabbit heart
SOLARO, R. J., MOIR, A. J. G., & PERRY, S. V. (1976) · Nature · doi:10.1038/262615a0 · Cited by 395 · see citing works
Role of Troponin I Proteolysis in the Pathogenesis of Stunned Myocardium
Gao, W. D., Atar, D., Liu, Y., et al. (1997) · Circulation Research · doi:10.1161/01.res.0000435855.49359.47 · Cited by 392 · see citing works
Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I
Wu, A. H. B., Feng, Y., Moore, R., Apple, F. S., McPherson, P., Buechler, K. F., & Bodor, G. S. (1998) · Clinical Chemistry · doi:10.1093/clinchem/44.6.1198 · Cited by 391 · see citing works
The effect of troponin I phosphorylation on the Ca2+-binding properties of the Ca2+-regulatory site of bovine cardiac troponin.
Robertson, S. P., Johnson, J. D., Holroyde, M. J., Kranias, E. G., Potter, J. D., & Solaro, R. J. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68355-9 · Cited by 357 · see citing works
Troponin I Degradation and Covalent Complex Formation Accompanies Myocardial Ischemia/Reperfusion Injury
McDonough, J. L., Arrell, D. K., & Eyk, J. E. V. (1999) · Circulation Research · doi:10.1161/01.res.84.1.9 · Cited by 318 · see citing works
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Extensive Troponin I and T Modification Detected in Serum From Patients With Acute Myocardial Infarction
Labugger, R., Organ, L., Collier, C., Atar, D., & Van Eyk, J. E. (2000) · Circulation · doi:10.1161/01.cir.102.11.1221 · Cited by 315 · see citing works
Self-citation
Preload Induces Troponin I Degradation Independently of Myocardial Ischemia
Feng, J., Schaus, B. J., Fallavollita, J. A., Lee, T., & Canty, J. M. (2001) · Circulation · doi:10.1161/01.cir.103.16.2035 · Cited by 288 · see citing works
Binding of Cardiac Troponin-I 147-163 Induces a Structural Opening in Human Cardiac Troponin-C ,
Li, M. X., Spyracopoulos, L., & Sykes, B. D. (1999) · Biochemistry · doi:10.1021/bi9901679 · Cited by 259 · see citing works
Breakdown and Release of Myofilament Proteins During Ischemia and Ischemia/Reperfusion in Rat Hearts
Eyk, J. E. V., Powers, F. G., Law, W. R., Larue, C., Hodges, R. S., & Solaro, R. J. (1998) · Circulation Research · doi:10.1161/01.res.82.2.261 · Cited by 234 · see citing works
Transgenic Mouse Model of Stunned Myocardium
Murphy, A. M., Kögler, H., Georgakopoulos, D., McDonough, J. L., Kass, D. A., Van Eyk, J. E., & Marbán, E. (2000) · Science · doi:10.1126/science.287.5452.488 · Cited by 228 · see citing works
Self-citation
Mapping of a second actin-tropomyosin and a second troponin C binding site within the C terminus of troponin I, and their importance in the Ca2+-dependent regulation of muscle contraction
Tripet, B., Eyk, J. E. V., & Hodges, R. S. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1200 · Cited by 204 · see citing works
In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts.
Takeishi, Y., Chu, G., Kirkpatrick, D. M., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2709 · Cited by 179 · see citing works
Covalent and Noncovalent Modification of Thin Filament Action
Metzger, J. M., & Westfall, M. V. (2004) · Circulation Research · doi:10.1161/01.res.0000110083.17024.60 · Cited by 179 · see citing works
Specific degradation of troponin T and I by μ-calpain and its modulation by substrate phosphorylation
Lisa, F. D., TULLIO, R. D., Salamino, F., et al. (1995) · Biochemical Journal · doi:10.1042/bj3080057 · Cited by 167 · see citing works
Cardiac Troponin I Mutants
Noland, T. A., Guo, X., Raynor, R. L., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25445 · Cited by 166 · see citing works
Intrinsic Myofilament Alterations Underlying the Decreased Contractility of Stunned Myocardium
Gao, W. D., Liu, Y., Mellgren, R. L., et al. (1996) · Circulation Research · doi:10.1161/01.res.78.3.455 · Cited by 158 · see citing works
The phosphorylation of troponin I from cardiac muscle
Cole, H. A., & PERRY, S. V. (1975) · Biochemical Journal · doi:10.1042/bj1490525 · Cited by 152 · see citing works
Phosphorylation of Both Serine Residues in Cardiac Troponin I Is Required to Decrease the Ca2+ Affinity of Cardiac Troponin C
Zhang, R., Zhao, J., & Potter, J. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30773 · Cited by 149 · see citing works
Long-Term caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function, and attenuates remodeling in rats with myocardial infarction
Chandrashekhar, Y., Sen, S., Anway, R., Shuros, A., & Anand, I. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.09.026 · Cited by 149 · see citing works
Evidence of myofibrillar protein oxidation induced by postischemic reperfusion in isolated rat hearts
Canton, M., Neverova, I., Menabò, R., Eyk, J. E. V., & Lisa, F. D. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00714.2003 · Cited by 148 · see citing works
Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction
Gao, C. Q. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00719-8 · Cited by 139 · see citing works
Altered Interactions Among Thin Filament Proteins Modulate Cardiac Function,
Solaro, J. R. (1996) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0021 · Cited by 135 · see citing works
Cardiac Troponin I Is Modified in the Myocardium of Bypass Patients
McDonough, J. L., Labugger, R., Pickett, W., Tse, M. Y., MacKenzie, S., Pang, S. C.-N., Atar, D., Ropchan, G. V., & Eyk, J. E. V. (2001) · Circulation · doi:10.1161/01.cir.103.1.58 · Cited by 129 · see citing works
Self-citation
Intracellular Localization and Functional Effects of P 21 -Activated Kinase-1 (Pak1) in Cardiac Myocytes
Ke, Y., Wang, Y. L., Pyle, W. G., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000111522.02730.56 · Cited by 115 · see citing works
Standardization of Cardiac Troponin I Assays: Round Robin of Ten Candidate Reference Materials
Christenson, R. H., Duh, S., Apple, F. S., Bodor, G. S., Bunk, D. M., Dalluge, J. J., Panteghini, M., Potter, J. D., Welch, M. J., Wu, A. H. B., et al. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.3.431 · Cited by 111 · see citing works
The C Terminus of Cardiac Troponin I Is Essential for Full Inhibitory Activity and Ca2+ Sensitivity of Rat Myofibrils
Rarick, H. M., Tu, X.-H., Solaro, R. J., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.43.26887 · Cited by 107 · see citing works
A Novel Mechanism for Myocardial Stunning Involving Impaired Ca 2+ Handling
Kim, S., Kudej, R. K., Yatani, A., et al. (2001) · Circulation Research · doi:10.1161/hh2101.098547 · Cited by 100 · see citing works
p21-Activated Kinase Increases the Calcium Sensitivity of Rat Triton-Skinned Cardiac Muscle Fiber Bundles via a Mechanism Potentially Involving Novel Phosphorylation of Troponin I
Buscemi, N., Foster, D. B., Neverova, I., & Eyk, J. E. V. (2002) · Circulation Research · doi:10.1161/01.res.0000035246.27856.53 · Cited by 92 · see citing works
Effects of Protein Kinase A Phosphorylation on Signaling between Cardiac Troponin I and the N-Terminal Domain of Cardiac Troponin C
Chandra, M., Dong, W., Pan, B., et al. (1997) · Biochemistry · doi:10.1021/bi9710129 · Cited by 88 · see citing works
Modulation of Thin Filament Activation by Breakdown or Isoform Switching of Thin Filament Proteins
Marston, S. B., & Redwood, C. S. (2003) · Circulation Research · doi:10.1161/01.res.0000105088.06696.17 · Cited by 86 · see citing works
Absence of Troponin I Degradation or Altered Sarcoplasmic Reticulum Uptake Protein Expression After Reversible Ischemia in Swine
Thomas, S. A., Fallavollita, J. A., Lee, T., et al. (1999) · Circulation Research · doi:10.1161/01.res.85.5.446 · Cited by 80 · see citing works
C-Terminal Truncation of Cardiac Troponin I Causes Divergent Effects on ATPase and Force
Foster, D. B., Noguchi, T., VanBuren, P., Murphy, A. M., & Eyk, J. E. V. (2003) · Circulation Research · doi:10.1161/01.res.0000099889.35340.6f · Cited by 77 · see citing works
Cardiac troponin I, isolated from‐bovine heart, contains two adjacent phosphoserines
Swiderek, K. M., Jaquet, K., Meyer, H. E., et al. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14286.x · Cited by 75 · see citing works
Phosphorylation-Induced Distance Change in a Cardiac Muscle Troponin I Mutant
Dong, W., Chandra, M., Xing, J. W., et al. (1997) · Biochemistry · doi:10.1021/bi9622276 · Cited by 75 · see citing works
Molecular and Integrated Biology of Thin Filament Protein Phosphorylation in Heart Muscle
Sumandea, M. P., Burkart, E. M., Kobayashi, T., de Tombe, P. P., & Solaro, R. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1302.004 · Cited by 75 · see citing works
Distinct Regions of Troponin I Regulate Ca2+-dependent Activation and Ca2+ Sensitivity of the Acto-S1-TM ATPase Activity of the Thin Filament
Eyk, J. E. V., Thomas, L., Tripet, B., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.16.10529 · Cited by 75 · see citing works
Overexpression of calpastatin by gene transfer prevents troponin I degradation and ameliorates contractile dysfunction in rat hearts subjected to ischemia/reperfusion
Maekawa, A. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00238-4 · Cited by 73 · see citing works
National Heart, Lung, and Blood Institute Clinical Proteomics Working Group Report
Granger, C. B., Eyk, J. E. V., Mockrin, S. C., & Anderson, N. L. (2004) · Circulation · doi:10.1161/01.cir.0000121563.47232.2a · Cited by 69 · see citing works
ASK1 Associates with Troponin T and Induces Troponin T Phosphorylation and Contractile Dysfunction in Cardiomyocytes
He, X., Liu, Y., Sharma, V. K., Dirksen, R. T., Waugh, R. E., Sheu, S., & Wang, M. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63647-4 · Cited by 68 · see citing works
Strategy for Analysis of Cardiac Troponins in Biological Samples with a Combination of Affinity Chromatography and Mass Spectrometry
Labugger, R., Simpson, J. A., Quick, M., Brown, H. A., Collier, C. E., Neverova, I., & Eyk, J. E. V. (2003) · Clinical Chemistry · doi:10.1373/49.6.873 · Cited by 49 · see citing works
Systematic mapping of regions of human cardiac troponin I involved in binding to cardiac troponin C: N‐ and C‐terminal low affinity contributing regions
Ferrières, G., Pugnière, M., Mani, J. C., Villard, S., Laprade, M., Doutre, P., Pau, B., & Granier, C. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01881-0 · Cited by 47 · see citing works
Calpain-mediated proteolytic cleavage of troponin I induced by hypoxia or metabolic inhibition in cultured neonatal cardiomyocytes
Kositprapa, C., Zhang, B., Berger, S. B., Canty, J. M., & Lee, T. (2000) · Molecular and Cellular Biochemistry · doi:10.1023/a:1007160702275 · Cited by 46 · see citing works
Modulation of Cardiac Troponin C−Cardiac Troponin I Regulatory Interactions by the Amino-terminus of Cardiac Troponin I
Abbott, M. B., Dong, W., Dvoretsky, A., et al. (2001) · Biochemistry · doi:10.1021/bi0100642 · Cited by 46 · see citing works
Conformation of the N-Terminal Segment of a Monocysteine Mutant of Troponin I from Cardiac Muscle
Dong, W., Chandra, M., Xing, J. W., et al. (1997) · Biochemistry · doi:10.1021/bi962226d · Cited by 42 · see citing works
Time-resolved tryptophan emission study of cardiac troponin I
Liao, R., Wang, C. K., & Cheung, H. C. (1992) · Biophysical Journal · doi:10.1016/s0006-3495(92)81685-5 · Cited by 41 · see citing works
Stunned peri-infarct canine myocardium is characterized by degradation of troponin T, not troponin I
COLANTONIO, D. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.04.006 · Cited by 37 · see citing works
The role of troponin abnormalities as a cause for stunned myocardium
Eyk, J. E. V., & Murphy, A. M. (2001) · Coronary Artery Disease · doi:10.1097/00019501-200108000-00002 · Cited by 28 · see citing works
Fluctuations between stabilizing and destabilizing electrostatic contributions of ion pairs in conformers of the c-Myc-Max leucine zipper
Kumar, S., & Nussinov, R. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20001201)41:4 · Cited by 23 · see citing works
Troponin I Proteolysis and Myocardial Stunning: Now You See It—Now You Don»t
Canty, J. M., & Lee, T. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2002.1531 · Cited by 21 · see citing works
Effect of Treatment on Ventricular Function and Troponin I Proteolysis in Reperfused Myocardium
Prasan, A. M., McCarron, H. C. K., Hambly, B. D., et al. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2002.1522 · Cited by 20 · see citing works
Degradation of rat cardiac troponin I during ischemia independent of reperfusion
Palmer, B. S., Klawitter, P. F., Reiser, P. J., & Angelos, M. G. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00149.2004 · Cited by 14 · see citing works
The Special Structure and Function of Troponin I in Regulation of Cardiac Contraction and Relaxation
Solaro, R. J. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-9029-7_36 · Cited by 12 · see citing works
The role of cardiac troponin in the recent redefinition of acute myocardial infarction.
Wu, A. H. B. (2004) · PubMed · Cited by 12 · see citing works
Effect of myocardial stunning on thiol status, myofibrillar ATPase and troponin I proteolysis
Kaplán, P., Matejovičová, M., Lehotský, J., et al. (2002) · Molecular and Cellular Biochemistry · doi:10.1023/a:1015514614183 · Cited by 5 · see citing works

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Authors: McDonough, J. L., & Van Eyk, J. E.
Affiliations: Johns Hopkins University (US)
Venue: Progress in Cardiovascular Diseases
Publisher: Elsevier BV
Published: 2004-11
Volume: 47
Issue: 3
Pages: 207-216
ISSN: 0033-0620 (ISSN-L)
DOI: 10.1016/j.pcad.2004.07.001
OpenAlex: W2040518216
Cited by: 62
References: 55
Citations by year: 2025: 3 · 2024: 1 · 2020: 3 · 2017: 5 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 4
FWCI: 5.01
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Cardiovascular Diseases (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (n01hv28180-13-0-0)
National Heart, Lung, and Blood Institute (N01 HV-28180)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords: troponin I, troponin T, cardiac biomarkers, acute myocardial injury, protein phosphorylation, protein oxidation, proteolysis, cardiac contractility
MeSH terms: Female, Forecasting, Humans, Male, Myocardial Contraction, Myocardial Infarction, Prognosis, Sarcomeres, Sensitivity and Specificity, Severity of Illness Index, Biomarkers, Troponin I

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Developing the next generation of cardiac markers: Disease-induced modifications of troponin I

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