Pashevin D. Role of proteasomal proteolysis in atherosclerosis modeling and stress

The mechanism of ubiquitin-dependent proteasomal degradation of proteins is one of the important regulators of some endocellular reactions, among which are regulation of a cellular cycle, cellular receptor formation, realization of apoptosis and autophagy processes, participation in antigens presentation, and other processes, that testifies to absolute importance of the normal functioning of this system for maintenance of vital functions of both cell and organism on the whole. Pathological changes of proteasomal proteolysis activity in one's turn may account for development of different pathological processes. The aim of our study was investigation of changes of proteasomal activity in heart tissue, aorta and isolated blood cells in atherosclerotic process modeling. Experiments were performed on 30 rabbits, witch were divided in two groups - control (10 rabbits) and experimental (20 rabbits). Animals of experimental group were getting feed with maintenance of 1% of cholesterol for 8 weeks. At eighth experimental week was performed blood sampling with following leukocytes separation and measurement of chemotrypsin-like (CTL), trypsin-like (TL) and peptidylglutamyl peptide-hydrolase (PGPH) proteasomal activities using spectrofluorimetric method. At the end of experimental term animals were subjected to euthanasia, heart tissue and aortas were homogenated, whereupon CTL, TL and PGPH proteasomal activities were measured. Obtained data testify to essential influence of hypercholesterol diet on proteasome activity both in aorta and heart tissue and blood leucocytes. Particularly in monocytes the TL activity of proteasome increased in 1.5 fold (P=0.45), CTL - in 1.9 fold (P=0.05) and PGPH - in 11.6 fold (P=0.0001). In lymphocytes changes show other character: TL activity of proteasome in lymphocytes decreased on 44% (P=0.095), while CTL and PGPH activities were changed insignificantly. In neutrophilic granulocytes as in monocytes TL and PGPH activities increased in 34% (P=0.4) and in 1.8 fold (P=0.031) respectively, while CTL activity practically didn't change. In aorta tissue increase of all activities was observed: TL activity of proteasomal complex increased in 3.2 fold in comparison with control (P=0.003), CTL activity - in 1.33 fold (P=0.11) and PGPH activities - in 1.8 fold (P=0.003). In heart tissue PGPH activity increased in 1.57 fold (P=0.007), CTL - on 20%, reliable changes in TL activity were absent. Obtained data testify that in aorta and heart tissues as well as in cells participating in development of atherosclerosis process and its complications (ischemic heart disease, myocardial infarction), proteasomal activity essentially changes, that is additional factor of pathogenesis, and using medicine witch selectively influence on proteasomal degradation it is possible to propose apparent angio- and cardioprotective effect.