[The dynamics of 2',5'-oligoadenylate synthetase activity in the nuclear and cytoplasmic fractions of human fibroblasts treated by double-stranded RNAs, by their complexes with DEAE-dextran and by type-I recombinant interferons. The ratio of double-stranded RNA-activated and -nonactivated froms of the enzyme].
Novel original preparations of double-stranded RNAs (dsRNAs), i.e. larifan, ridostin and rifastin, and recombinant alpha 2- and beta-interferons promising for the clinical use were studied. The size and morphology of the dsRNAs in the preparation composition, the dynamics of their induction of interferon and the antiviral state in human fibroblasts and the effect of the DEAE dextran polycation on the activity of the dsRNAs were specified. For the first time the dynamics of 2',5'-oligoadenylate synthetase activity in the nuclei and cytoplasm of the human fibroblasts treated with the dsRNAs of different origin and their complexes with DEAE dextran was defined. To elucidate the specific features of the mechanism of antiviral action of dsRNAs and interferon, the relation of the 2',5'-oligoadenylate synthetase activity to dsRNAs was investigated. In the cells treated with dsRNAs and DEAE dextran there were an early activation of the enzyme and predominance of the enzyme activated forms requiring no addition of poly I.poly C to the reaction mixture. The results were indicative of possible intracellular activation of its isoforms, similar to that in the cells treated with interferon and contaminated with viruses. All the tested preparations of dsRNAs and interferons induced an increase in the activity of 2',5'-oligoadenylate synthetase both in the cytoplasm and the nuclei of human fibroblasts. The same ability was observed in DEAE dextran which is likely to be one of the causes of the increase in dsRNAs antiviral activity under its effect.
Sokolova
T M
TM
Antonov
A Iu
AIu
Makhov
A M
AM
D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects* / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D003593:Cytoplasm / Q000187:drug effects* / Q000201:enzymology; D003637:DEAE-Dextran / Q000494:pharmacology*; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology* / Q000648:ultrastructure; D011994:Recombinant Proteins
D004338:Drug Combinations; D007370:Interferon Type I; D007527:Isoenzymes; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D003637:DEAE-Dextran; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C
Dinamika aktivnosti 2',5'-oligoadenilatsintetazy v iadernoĭ i tsitoplazmaticheskoĭ fraktsiiakh fibroblastov cheloveka, obrabotannykh dvuspiral'nymi RNK, kompleksami ihk s DEAE-dekstranom i rekombinantnymi interferonami tipa I. Sootnoshenie aktivirovannykh i neaktivirovannykh dvuspiral'nymi RNK form fermenta.