Posttranslational phosphorylation and fragmentation of cardiac troponin T: mechanisms and significance

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Abstract

Among a very significant number of possible variants of posttranslational modifications (PTM) affecting the contractile function of the myocardium, the most significant effect is exerted by posttranslational phosphorylation of protein components of the contractile apparatus. This type of PTM is carried out due to the action of kinase enzymes (phosphotransferases) that catalyze the transfer of a phosphate group to amino acid residues of proteins of the contractile apparatus. A change in the phosphorylation activity leads to a change in the function of the corresponding modified protein, which is accompanied by a change in the contractile function of the entire myocardium. At the same time, the phosphorylation activity of certain contractile proteins can change both in physiological conditions and in some cardiovascular diseases (CVD), including heart failure, acute myocardial infarction and cardiac arrhythmias. In addition, with these pathological conditions, the activity of proteolytic enzymes that cause fragmentation of protein molecules significantly changes. The purpose. To systematize information about the main mechanisms of posttranslational phosphorylation and fragmentation of the cardiac troponin T (cTnT) molecule and note their importance in the pathogenesis and diagnosis of CVD. Material and methods. Analysis of the main foreign and domestic sources on PubMed/Medline, Embase, RSCI/elibrary databases over the past 30 years. Results. According to the results of the review, a significant effect of the discussed PTMs on the pathophysiology and laboratory diagnosis of CVD was shown: 1) an increase in cTnT phosphorylation is mainly accompanied by a decrease in myocardial contractile function; the level of phosphorylated cTnT molecules in blood serum may reflect the status of intracellular phosphorylation, and, accordingly, be used for diagnostic and prognostic purposes; 2) fragmentation of the cTnT molecule into smaller fragments promotes earlier release from cardiomyocytes, and by identifying these fragments using immunoassays, early diagnosis of CVD can be improved; these small cTnTfragments can also pass through a hematosalivary and glomerular filter, allowing the use of saliva and oral fluid as a non-invasively obtained biological material, 3) the cleavage of the cTnT molecule by the enzyme thrombin in the myocardium of patients sufferingfrom cardiomyopathy can be considered as an additional pathophysiological mechanism that disrupts the contractile function of the myocardium.

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About the authors

Aleksey Mikhailovich Chaulin

Samara Regional Cardiology Dispensary; Samara State Medical University

Author for correspondence.
Email: alekseymichailovich22976@gmail.com

post-graduate student, assistant of the department of histology and embryology; MD, doctor of clinical of laboratory diagnosis

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2. Diagram of the structure of the TTC and its structural changes during contraction and relaxation Note. A – schema of the structure of the sarcomere. B – structure of the thin thread when the heart muscle relaxes, C-the structure of the thin thread when the heart muscle contracts. TnT – troponin T; TnI – troponin I; TnC – troponin C.

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