Yu.Yu. Kondratiuk, A.I. Korneliuk, V.I. Bobik, L.L. Sidorik, D.V. Riabenko Autoimmune reactions against tyrosyl-tRNA synthase and its particular structural modules in dilated cardiomyopathy.

The aim of investigation was to study the expression of tyrosyl-tRNA synthase (TyrRS) in myocardium and to examine the peculiarities of autoimmune reactions against full-size TyrRS and its N- and C-terminal modules in
dilated cardiomyopathy (DCM). Recombinant proteins full-size TyrRS and its N- and C-terminal modules were isolated from the bacterial strains based on Escherichia coli BL21(DE)pLysE. TyrRS expression in myocardium
was identified by Western-blot analysis in pathomorphologic specimens of three DCM-affected human myocardia and samples of left ventricular myocardium of three practically healthy men who died from casual
trauma as a control. The level of specific circulating antibodies (Abs) against full-size TyrRS and its C- and N-terminal modules were measured by ELISA method in sera of 30 DCM patients with congestive heart failure.
Sera of 20 healthy donors were examined as a control. In order to study the effect of auto-Abs on TyrRS enzymatic activity we purified these Abs from DCM patients’ sera with immunoaffine chromatography and
analyzed their influence on the parameters of aminoacylation reaction of cognated tRNA catalyzed by TyrRS. The increased expression (by 43%) of TyrRS was revealed in total lysates and especially in nuclear subfraction
of DCM-affected cardiomyocytes compared to control. The increased levels of auto-Abs against full-size TyrARS (by 20.5%), against its N-terminal (catalytic) modules (by 21.1%) and C- (non-catalytic) modules (by
29.1%) were found in blood serum of DCM patients, compared with healthy donors.

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