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Information × Registration Number 0219U000538, 0113U002779 , R & D reports Title Investigation of the effect of oligonucleotides on the signaling proteins and gene expression of innate immunity popup.stage_title Head Tkachuk Zenoviy Yuriyovich, Registration Date 06-02-2019 Organization Institute of Molecular Biology and Genetics of NASU popup.description2 A mass spectrometric analysis of oligoribonucleotides (ORNs) composition of yeast RNA has been carried out, the main part of which is found in heterogeneous ORNs in the length from 4 to 7 nucleotides. The efficiency of the chromatographic separation of ORNs by their length is confirmed. MALDI-Tof-Tof mass spectrometry of ORNs indicate that peaks on the chromatogram belong to oligoribonucleotides of different lengths, namely, a minor fraction of 2 to 4 nucleotides, a dominant fraction of 4 to 7 nucleotides and a small fraction of 10 to 15. The presence of ORNs complexation with mannitol is shown, in contrast to its analogue of sorbitol and lactose. Optimal ratios of complex formation in the ORNs-ligand system in the mixture of RNA: mannitol, which is 3:1, according to the complex formation of about 100%, were determined using the methods of IR and Fourier-transform spectroscopy. Many spectral methods demonstrated the ability of ORNs and their derivatives to alter the conformation of interferon alpha-2b and its thermal stability. Analysis of CD spectra using the CDNN software has shown that conformational changes in the protein under the influence of ORN drugs occur predominantly in the alpha-spiral, indicating a change in the secondary structure of the protein. The obtained data testify in favor of the assumption of the possibility of binding of ORNs outside the active center of proteins and their ability to change the conformation of proteins and their structure. We found that the ORNs-d-M reduced the influenza-induced up-expression of Toll-like receptors (TLRs) (tlr3, tlr7, tlr8), nuclear factor NF-kB (nfkbia, nfnb1), cytokines (ifne, ifnk, ifna2, ifnb1, ifn?, il6, il1b, il12a, tnf), chemokines (ccl3, ccl4, ?cl5, cxcl9, cxcl10, cxcl11), interferon-stimulated genes (oas1a, oas2, oas3, mx1), and pro-oxidation (nos2, xdh) genes. The ORNs-d-M inhibited the mRNA overexpression of tlr3, tlr7, and tlr8 induced by the influenza virus, which suggests that they impair the upregulation of NF-kB, cytokines, chemokines, ISGs, and pro-oxidation genes induced by the influenza virus by inhibiting activation of the TLR-3, TLR-7, and TLR-8 signaling pathways. By impairing activation of the TLR-3, TLR-7, and TLR- 8 signaling pathways, the ORNs-d-M can modulate the innate immune response to an influenza virus infection. The ORNs-D-M complex has a protective effect on the model of TAA-induced acute toxic lesion of the liver. The main mechanisms by which this complex protects the liver from a toxic lesion associated with anti-inflammatory properties and the ability to modulate NF- kB signaling. Since NF-kB is the central transcription regulator for regulating the expression of inflammatory cytokines (TNF-alpha, IL-6), we assume that by suppressing the activation of NF- kB, they reduce the expression of TNF-alpha and IL-6 mRNA. Product Description popup.authors Вівчарик Марина Михайлівна Левченко Світлана Миколаївна Марчишак Тетяна Вікторівна Мельнічук Наталія Сергіївна Ніколаєв Роман Олександрович Семернікова Лариса Іванівна Скоробогатов Олександр Ткачук Зеновій Юрійовичк. Ткачук Лариса Володимирівна Щодрий Володимир Богданович Яковенко Тетяна Григорівна popup.nrat_date 2020-04-02 Close