Kravchenko O. The role of Ca2+-dependent messenger system in colitis-associated carcinogenesis development

The dissertation is dedicated to the study of the functional state of major Ca2+-dependent signal pathway elements (phospholipase C, phospholipids, Ca2+, protein kinase C, Ca2+/calmodulin-dependent protein kinase) and individual components of another messenger systems (NO-synthase, protein kinase A, protein kinase G, tyrosine protein kinase) under colitis- associated carcinogenesis. The conducted study provided us with the proof that on the third day of inflammation development under the experimental ulcerative colitis, the statically evident decrease of phosphatidylcholine and phosphatidylethanolamine in cytoplasmic membranes of large intestine mucosa epithelial cells of laboratory rats was observed. The like dynamics change of major structural membrane components was preserved in all the latter periods of inflammation. Such a disfunction was accompanied by the increase of one of the key ferment activity, which is responsible for the phospholipids hydrolyze - phospholipase C. Analysis of Ca2+-dependent protein kinase activity in plasmatic membranes and cytosol of epithelial cells of the large intestine, revealed that protein kinase C as well as calmodulin-dependent protein kinase activity have decreased in membranes on the 1-3-rd days of the experiment, but these data remained almost unchanged in cytosol. On a latter stages of the inflammation and during the carcinogenesis initiation, hyperactivation the aforementioned kinases in cytosol was noticed, together with the alternate fluctuation of their activity in fraction of plasmatic membranes.The activity of cyclonucleothyde-dependent protein kinases was similar to the aforementioned dynamics changes in cytosol and membrane of colonocytes. Alongside with this, the activity of tyrosine protein kinase in the inflammation period desreased in cytosol and increased in membranes. In the following stages of oncopathology development, the activity of cytosol forms of tyrosine kinase increased considerably. The received results prove us the principal significance of the dysfunction of signal cascades in development of inflammation and in stimulated malignant large intestine mucosa cells degeneration.