Tkachenko Viktoriya Andriyivna


Oxidative modification of proteins and ways of their prevention in conditions of experimental myocardial ischemia


The dissertation is devoted to the study of non-enzymatic post-translational
modifications of proteins (OMP) and identifying ways to prevent the negative effects
of these processes under conditions of development of carbonyl-oxidative stress
(СOS) in rats with experimental myocardial ischemia. Indicators of OMP, the level of
advanced glycation end products (AGEs), AGE-R3 and the activity of proteolytic and
antioxidant enzymes in rats with epinephrine-induced myocardial ischemia and
pituitrine-isoprenaline-induced myocardial damage (PIMD) were investigated in the
work. Exogenous antioxidants, such as quercetin and 2-oxoglutarate; hypoglycemic
drug as aminoguanidine and drugs that can affect the processes of degradation of
modified proteins as doxycycline and epleranone to assess the possible ways of
pharmacological correction of metabolic disorders arising from СOS were used.
All tested drugs reduce СOS, by activating the ways of ROS neutralization and
dicarbonyl compounds inactivation, by regulating the activity of enzymes of the
antioxidant system (the level of SOD in erythrocytes of PIMD- rats almost did not
change, activity of catalase in plasma decreased by nearly 5 times, while in contrast,
the activity of glutathioneperoxidase in erythrocytes, increased by 1,5 times), and
changing in the proteolytic/anti-proteolytic balance (MMP9 activity and α2-
macroglobulin level significantly increases in blood, whereas MMP2 activity and α1-
proteinase inhibitor level increases in heart) and excretion of OMP products.
We established that effects of small doses of doxycycline are comparable to or
are greater than the effect of classical antioxidants, such as aminoguanidine and
quercetin, and the use of this drug is promising for the treatment of postinfarction
heart failure.
Investigation of the level of AGE-R3 level, which has AGEs scavenger-
receptor properties, of allowed us to establish its ability to the olygomerization and
redistribution of AGER-3 forms in experimental myocardial ischemia. We also
showed, that antioxidants and doxycycline reduce, the amount of all AGE-R3 forms,
except for the tetrameric AGE-R3. This form is significantly increased even in
comparison to the PIMD-group. The amount of mono-AGE-R3 decreased
tremendously and the level of its oligomeric forms increased after the treatment with
Q. In contrast, amount of mono-AGE-R3 forms increased in 5 times and its
oligomerization reduced after the treatment with Е.
The results of this study this expand understanding of the molecular
mechanisms underlying the development of cardiovascular diseases and its
complications, and provide important information regarding the ways of their
metabolic-based correction.
Key words: antioxidant system, proteolysis, myocardial ischemia, oxidative-
carbonyl stress, cardioprotective medications, advanced glycation end products,
proteolysis , оxidative modification of proteins, receptors.

Defence Date


Dissertation File

Autosummary File