Current Ph.D. thesis is dedicated to the investigation of the composition and properties of supramolecular structures and biochemical processes on the level of plasma membrane on apoptosis and eryptosis.
Changes in plasma membrane lipid order on apoptosis are similar to one caused by the cholesterol extraction, 7-ketocholesterol enrichment, and sphingomyelin hydrolysis, which signifies the essential plasma membrane reorganization on programmed cell death of nucleated cells.
For the first time, the link between caspase-3 activation and the decrease of the Lo-phase in outer plasma membrane leaflet on the early steps of apoptosis in HeLa cells was shown.
It was shown that in Jurkat cells and in human erythrocytes the exposure of both PS and PE to outer plasma membrane leaflet takes place on programmed cell death, with lower values of PE dynamics on eryptosis. Nevertheless, despite the strong visual similarities of apoptosis and eryptosis, the red blood cells share smaller decrease of Lo-phase in outer plasma membrane leaflet.
The morphological features of plasma membrane supramolecular organization during its vesiculation on apoptosis and eryptosis were investigated. In all studied cells (HeLa, Jurkat, human erythrocytes), in contrast to the main area of the plasma membrane, the significant amount of Ld-phase in outer vesicles leaflet was observed. However, it is worth to mention, that the erythrocytes' vesicles are more ordered.
The difference in lipid order between plasma and membranes of organelles in nucleated HeLa and Jurkat cells was shown. It is important that after apoptosis induction the difference in Lo-phase and cholesterol content between these membranous structures becomes negligible. In a strong contrast to nucleated cells, red blood cells did not share this dynamics. Moreover, the increase of the lipid order for both monolayers of the plasma membrane was observed on eryptosis.
For the first time it was shown that in a strong contrast to nucleated cells, where the lipid packing density decreases on apoptosis (particularly, in the regions of apoptotic bodies), the red blood cells on eryptosis appear with denser lipid organization of the plasma membrane.
Erythrocytes share similar plasma membrane penetration ability for nanoparticles on eryptosis in comparison to intact cells, while HeLa cells accumulate their higher amount even on early steps of apoptosis. The increase of lateral and integral plasma membrane lipid packing density on eryptosis is confirmed additionally by the decrease of the acid hemolysis velocity.
In summary, according to the aim and tasks of the research, the structural-functional properties of the plasma membrane on apoptosis and eryptosis were studied and the significant difference was found. Thus, in contrast to apoptosis in nucleated cells, on eryptosis, the loss of lipid order in biomembranes is almost negligible. We suggest that in nucleated cells the additional lipid exchange between the plasma and intracellular membranes, possessing much lower lipid order and cholesterol content, may contribute to such dramatic changes. Consequently, the apoptotic vesicles appear of different origin, being derived from different membrane structures. By contrast, erythrocytes are devoid of intracellular membranes and their relatively high level of lipid order is retained on eryptosis.
