INFLUENCE OF COMPLEXES OF ANTISENSE-OLIGONUCLEOTIDES WITH POLYMERIC CARRIERS ON CONTENT OF CELLULAR PRION IN RAT ORGANS

N. U. Susol


DOI: http://dx.doi.org/10.30970/sbi.1101.515

Abstract


Сonjugates of antisense ODN (asODN) with three newly synthesized samples (MP-2, MP-2, MP-27) of polymer carriers based on DMAEM have been studied. It was found that these best conjugates could be created by mixing 0.5 % solution of polymers with asODN. It was found that a survival time of sperm cells was 96 h under action of 0.5 % solution of polymers MP-2 and MP-3. The survival time of sperm cells was increseaced to 120 h at treatment of cells with 0.5% solution of MP-27 polymer. That had lower cytotoxicity comparing to MP-2 and MP-3 polymers. The effectiveness of transporting system of these conjugates and its influence on cellular prion protein were studied. The results of Western-blot analysis showed that the injection of asODN conjugates with DMAEM into rats caused a decrease in PrPC in spleen, intestines and brain. AsODN conjugates injected with MP-27 carriers demonstrated that the content of cellular prion in spleen was decreased by 9 % after 2 days and by 32 % after 7 days. The contents of cellular prion in the intestine decreased by 38 % after 2 days and by 55 % after 7 days. The content of cellular prion in brain tissues decreased by 28 % after 2 days and by 34 % after 7 days, respectively. Thus, complexes of asODN with DMAEM descrease the  content of cellular prion in rat organs and tissues.


Keywords


cellular prion, brain, intestines, spleen, oligonucleotides, DMAEM conjugates

References


1. European convention for the protection of vertebrate animals used for experimental and other scientific purposes. Strasburg: Council of Europe, 1986. 52 p.

2. Friberg K.N. Hung G., Wancewicz Ed. et al. Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice. Published online 7 February 2012.

3. Fischer M., Appelhans D., Schwarz S. Influence of surface functionality of poly(propylene imine) dendrimers on protease resistance and propagation of the scrapie prion protein. Biomacromolecules, 2010, 11(5): 1314-1325.
https://doi.org/10.1021/bm100101s
PMid:20405854

4. Hudziak R.M., Barofsky E., Barofsky D.F. Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation. Antisense Nucleic Acid Drug. Dev, 1996; 6(4): 267-272.
https://doi.org/10.1089/oli.1.1996.6.267
PMid:9012862

5. Ivanytska L.A., Stadnyk V.V, Martin U.V. Efficient method of prion gene silencing in vitro and in vivo by antisense-oligodeoxynucleotides conjugated with new dimethylaminoethylmethacrylate oligoelectrolite. Studia Biologica, 2011; 5(3): 77-88. (In Ukrainian)
https://doi.org/10.30970/sbi.0503.168

6. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage. Nature, 1970; 4(227); 680-685.
https://doi.org/10.1038/227680a0
PMid:5432063

7. Lowry O.H., Rosebrough N.J., Farr A.L. Protein measurement with the Folin phenol reagent. J. Biol. Chem, 1951; 193(1): 265-275.

8. Mikush (Susol) N.U., Vlizlo V.V., Zayichenko S.O. Research facilities antysens-oligonucleotides with newly-synthezied oligoelectrolyte carriers based DMAEM. Visnyk of Lviv University. Biological Series, 2016; 1: 50-56. (In Ukrainian)

9. Susol N.U., Martin U.V., Kuzmina N.V, Vlizlo V.V. Histostructure of white rats organs after used newly polymeric-oligoelectrolitics carriers with asODN. Animal Biology, 2016; 18(3): 91-95. (In Ukrainian)
https://doi.org/10.15407/animbiol18.03.091

10. Supattapone S., Wille H., Uyechi M.R. Branched polyamines cure prion-infected neuroblastoma cells. J. Virol, 2001; 75(7): 3453-3461.
https://doi.org/10.1128/JVI.75.7.3453-3461.2001
PMid:11238871 PMCid:PMC114138

11. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA, 1979; 76(9): 4350-4354.
https://doi.org/10.1073/pnas.76.9.4350
PMid:388439 PMCid:PMC411572

12. Vlizlo V.V., Ivanytska L.A., Mikush (Susol) N.U. Development of drugs for the treatment and prevention of prion infection. BACAC, 2014, 24-28 March, Tbilisi, Georgia, p. 23.


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