Klimochkina E. Biochemical mechanisms of apoptosis of distinct diffentiation levels cells

The dissertation deals with determination of the role of apoptosis modulation and the place of opiate receptors and mitochondrial К+АТФ - dependent chanels in biology of cells with different diffentiation levels. The work is focused on research into and comparison of the role of basic regulatory systems of cells, which are at differnt levels of differentiation in the processes of apoptosis modulation. In the course of this research examinations in 33 trial groups of mononuclear cells and 27 groups of МSC (mesenсhimal stem cells) have been carried out, which showed different state of opiate receptors and mitochondrial К+АТФ - dependent channels. The analysis of morphological detection of apoptosis has been performed with the use of nuclear stain Hoechst 33342, estimation of DNA fragmentation, stable metabolite of nitric oxide, sphingosine, vital signs of energy metabolism, kinesis of SOD (superoxide dismutase), nuclear magnetic resonance - relaxation. Dependency of nitric oxide production in МSC and interrelation of apoptosis and proliferation on the type of activated opiate receptors has been ascertained for the first time, enhancement of their anti-apoptotic effect with the help of dexamethasone, accompanied by SOD proplasia and drop in the level of sphingosine has been demonstrated. The role of mitochondrial К+АТФ - dependent channels in МSC biology has been proved through demonstration of proliferative activity enhancement and drop in the level of apoptosis in the event of a blocking, and diminution in proliferation against the background of.apoptotic processes slight growth in case of their activation. Protective effect of opiate receptors agonists on mononuclear cells in the conditions of hormone-dependent apoptosishas been detected., it has been revealed that it is more pronounced in case of selective stimulation of these receptors, accompanied with drop in SOD level. The data on unambiguous dependence of the direction of action of opiate receptors (pro-apoptotic and anti-apoptotic) on the condition of mitochondrial К+АТФ - dependent channels has been obtained, both in the conditions of hormone-dependent apoptosis and without it.