Mayor K. Level of cellular prion in the peripheral part of rats prion replicating system under the influence of preparations from glycosaminoglycan group

Current thesis is focused on the investigation of the cellular prion (PrPС) level in the key peripheral prion replicating organs of rats – spleen, small intestine and skeletal muscles in normal conditions and under the action of heparin and pentosan polysulfate (PPS). Investigation of the general PrPС level showed that in estimated organs the highest level of cellular prion was observed in spleen and small intestine of rats, while in skeletal muscles level of PrPС expression reached only 70 % from that in spleen. 16 It was shown that predominant molecular form of cellular prion in spleen and small intestine of rats was PrPС2, otherwise to PrPС1 that was most poor represented molecular form in listed organs. Only in skeletal muscles PrPС1 form was dominating. PPS and heparin were chosen as agents able to interact with PrPc in vitro and were checked whether they will interact with PrPС in vivo causing decrease of its level in the tissues of prion replicating system peripheral organs. Intramuscular injections of heparin and PPS showed promising results for decrease of PrPС level in all studied peripheral organs of rats. Moreover, PPS inhibited PrPС expression level injected in much lower active doses comparing to heparin. Heparin in applied doses had no influence on the pattern of the PrPС molecular forms, while PPS injected in doses 0,1 and 0,5 mg/kg*day caused appearance of molecular form PrPС3. Used compounds were checked on their influence on the prion-dependent indexes. Heparin caused decrease in Cu2+/Zn2+-superoxide dismutase activity and alterations in coagulation system. Nevertheless heparin possessed no influence on copper and zinc level in studied organs and tissues. PPS had no influence on the activity of Cu2+/Zn2+-dependent SOD and coagulation system, while causing increase of copper and zinc concentration in all studied organs. PT-PCR analysis was used to estimate the level of PrPС mRNA after PPS injections. Investigation was shown that decrease of PrPС level is not caused by alterations in mRNA synthesis-degradation ratio. DNA comet assay showed that PPS in applied doses did not induce any cytotoxic effect on splenocytes. In current research was demonstrate that PPS is an effective and promising PrPС inhibiting agent which in tested doses posses no side effects in vivo and can be used for the therapy and prophylaxis of prion infections.