(2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.
- 1 August 1983
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 80 (15) , 4609-4613
- https://doi.org/10.1073/pnas.80.15.4609
Abstract
(2''-5)Oligoadenylate synthetase [(2''-5'')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2''p)n5''A [collectively referred to as (2''-5'')A], has previously been described in rat liver cells, where its concentration varied with the growth status of this organ, i.e., it decreased during the early phase of rat liver regeneration after partial hepatectomy. Because double-stranded RNA, the only known activator of this enzyme, has been detected in rat liver nuclei, (2''-5'')A synthesis could occur in this tissue in vivo. Analysis of rat liver cell extract after HPLC [high pressure liquid chromtography] by the endonuclease-based radiobinding assay revealed several components with retention times similar to (2''-5'')A trimer- and tetramer-like material. A further characterization of these compounds by their susceptibility to alkaline phosphatase and snake venom phosphodiesterase, their resistance to micrococcal nuclease and their ability to activate an endonuclease indicated the natural occurrence of oligonucleotides indistinguishable from authentic (2''-5'')A in rat liver cells. Using the combination of the radiobinding assay and a simplified (2''-5'')A extraction procedure that does not involve HPLC it was further shown that the early drop of (2''-5'')A synthetase activity during rat liver regeneration was accompanied by a similar decrease in intracellular (2''-5'')A concentration. The 3 characteristic phases of the (2''-5'')A synthetase kinetics during the first 40 h of liver regeneration were mimicked by the kinetics of the synthesis of the (2''-5'')A oligonucleotides themselves: between 6 and 20 h after hepatectomy, there was a sharp decrease in (2''-5'')A concentration; between 20 and 24 h, the concentration of (2''-5'')A reached a minimum; at 36 h or after the 1st wave of DNA synthesis (the major event of liver regeneration), the (2''-5'')A concentration returned to normal. In this characterization of the (2''-5'')A oligonucleotide family in a functional tissue of an animal that had not been previously treated with interferon or infected with virus, the data are compatible with a physiological role of the (2''-4'')A system acting as an intracellular component of the regulatory mechanisms leading to cell proliferation or differentiation.This publication has 37 references indexed in Scilit:
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