Cardiac troponins may be irreversibly modified by glycation: novel potential mechanisms of cardiac performance modulation
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2018-12-01
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Scientific Reports
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NATURE PORTFOLIO
Melbourne Authors
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Physiology
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Journal Article
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Janssens, J. V., Ma, B., Brimble, M. A., Van Eyk, J. E., Delbridge, L. M. D. & Mellor, K. M. (2018). Cardiac troponins may be irreversibly modified by glycation: novel potential mechanisms of cardiac performance modulation. Scientific Reports, 8 (1), https://doi.org/10.1038/s41598-018-33886-x.
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Abstract
Dynamic movements of the cardiac troponin complex are an important component of the cardiac cycle. Whether cardiac troponins are subjected to irreversible advanced glycation end-product (AGE) modification is unknown. This study interrogated human and rat cardiac troponin-C, troponin-I and troponin-T to identify endogenous AGE modifications using mass spectrometry (LC-MS/MS). AGE modifications were detected on two amino acid residues of human troponin-C (Lys6, Lys39), thirteen troponin-I residues (Lys36, Lys50, Lys58, Arg79, Lys117, Lys120, Lys131, Arg148, Arg162, Lys164, Lys183, Lys193, Arg204), and three troponin-T residues (Lys107, Lys125, Lys227). AGE modifications of three corresponding troponin-I residues (Lys58, Lys120, Lys194) and two corresponding troponin-T residues (Lys107, Lys227) were confirmed in cardiac tissue extracts from an experimental rodent diabetic model. Additionally, novel human troponin-I phosphorylation sites were detected (Thr119, Thr123). Accelerated AGE modification of troponin-C was evident in vitro with hexose sugar exposure. This study provides the first demonstration of the occurrence of cardiac troponin complex AGE-modifications. These irreversible AGE modifications are situated in regions of the troponin complex known to be important in myofilament relaxation, and may be of particular pathological importance in the pro-glycation environment of diabetic cardiomyopathy.