Cardiac troponins may be irreversibly modified by glycation: novel potential mechanisms of cardiac performance modulation
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...
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Veröffentlicht in: | Scientific reports 2018-10, Vol.8 (1), p.16084-14, Article 16084 |
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Sprache: | eng |
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Zusammenfassung: | 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 (Lys
6
, Lys
39
), thirteen troponin-I residues (Lys
36
, Lys
50
, Lys
58
, Arg
79
, Lys
117
, Lys
120
, Lys
131
, Arg
148
, Arg
162
, Lys
164
, Lys
183
, Lys
193
, Arg
204
), and three troponin-T residues (Lys
107
, Lys
125
, Lys
227
). AGE modifications of three corresponding troponin-I residues (Lys
58
, Lys
120
, Lys
194
) and two corresponding troponin-T residues (Lys
107
, Lys
227
) were confirmed in cardiac tissue extracts from an experimental rodent diabetic model. Additionally, novel human troponin-I phosphorylation sites were detected (Thr
119
, Thr
123
). 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. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-018-33886-x |