Kondratiuk I. Immunochemical studies of mammalian tyrosyl-tRNA synthetase and its involvement to immunopathogenesis of dilated cardiomyopathy

The present study is dedicated to the investigation of new properties and noncanonical functions of a key enzyme of first phase protein biosynthesis - tyrosyl-tRNA synthetase. The development of the new methogical approaches to bacterial expression of recombinant synthetase and its individual N-terminal catalytic and C-terminal non-catalytic modules. Polyclonal and autoantibodies against full-leng tyrosyl-tRNA synthetase was obtained and tested their effects on enzymatic activity of the protein in the aminoacylation reaction. Their opposite effect have been shown. For the first time it has been shown the features of synthetase expression in cardiomyocytes of dilated cardiomyopathy in humans and in the dynamics of induced disease in animal models. The quantitative and qualitative changes in enzyme expression of the disease was established. The changes of quantitative levels of autoantibodies against full-leng synthetase and its individual N-terminal catalytic and C-terminal non-catalytic modules was founed. The increase level of autoantibodies in blood serum of people with different manifestations of heart failure and in serum of model mice in progression of heart disease was shown.