Oligoadenylate and Cyclic AMP: Interrelation and Mutual Regulation

Itkes, A.V.

doi:10.1007/978-3-642-78549-8_12

Cited by 7 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cyclic AMP also induced 2-5A synthetase mRNA on a transcriptional level (Itkes et al, 198413). Although there are no sites in the 2-5A synthetase 5'-flanking region analogous to the CAMP-responsive element TGACGTCA, several other potential transcription binding factor sites do exist (Itkes, 1994). Interleukin (IL)-6 has also been found to exhibit synergism with Type I IFN in Ml cells, possibly by inducing DNA binding factors (Cohen et al,199 1).…”

Section: Mmt P-monomethoxytritylmentioning

confidence: 99%

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Player

Torrence

1998

Pharmacology & Therapeutics

245

195

View full text Add to dashboard Cite

The 2-5A system is an RNA degradation pathway that can be induced by the interferons (IFNs). Treatment of cells with IFN activates genes encoding several double-stranded RNA (dsRNA)-dependent synthetases. These enzymes generate 5'-triphosphorylated, 2',5'-phosphodiester-linked oligoadenylates (2-5A) from ATP. The effects of 2-5A in cells are transient since 2-5A is unstable in cells due to the activities of phosphodiesterase and phosphatase. 2-5A activates the endoribonuclease 2-5A-dependent RNase L, causing degradation of single-stranded RNA with moderate specificity. The human 2-5A-dependent RNase is an 83.5 kDa polypeptide that has little, if any, RNase activity, unless 2-5A is present. 2-5A binding to RNase L switches the enzyme from its off-state to its on-state. At least three 2',5'-linked oligoadenylates and a single 5'-phosphoryl group are required for maximal activation of the RNase. Even though the constitutive presence of 2-5A-dependent RNase is observed in nearly all mammalian cell types, cellular amounts of 2-5A-dependent mRNA and activity can increase after IFN treatment. One well-established role of the 2-5A system is as a host defense against some types of viruses. Since virus infection of cells results in the production and secretion of IFNs, and since dsRNA is both a frequent product of virus infection and an activator of 2-5A synthesis, the replication of encephalomyocarditis virus, which produces dsRNA during its life cycle, is greatly suppressed in IFN-treated cells as a direct result of RNA decay by the activated 2-5A-dependent RNase. This review covers the organic chemistry, enzymology, and molecular biology of 2-5A and its associated enzymes. Additional possible biological roles of the 2-5A system, such as in cell growth and differentiation, human immunodeficiency virus replication, heat shock, atherosclerotic plaque, pathogenesis of Type I diabetes, and apoptosis, are presented.

show abstract

Section: Mmt P-monomethoxytritylmentioning

confidence: 99%

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Player

Torrence

1998

Pharmacology & Therapeutics

245

195

View full text Add to dashboard Cite

show abstract

Section: Anti-hiv Activity Ofpropentofy/linementioning

confidence: 87%

“…The involvement of cAMP in the control of 2~5A metabolism has been hypothesized already (Itkes, 1994). The increase in intracellular cAMP level in the presence of the cAMP phosphodiesterase inhibitor theophylline was found to be associated with an increase in 2-5A synthetase activity and an inhibition of the 2-5A-degrading 2'-phosphodiesterase activity (Itkes et al, 1984;Itkes, 1994). There is also evidence that the antiproliferative Although it is likely in view of our resultsthat the decrease in 2-5A synthetase activity and protein following HIV infection is due to the HIV-caused decrease in 2-5A synthetase mRNA level, proteolytic degradation of the enzyme might be possible, too.…”

Section: Anti-hiv Activity Ofpropentofy/linementioning

confidence: 89%

Modulation of the Antiviral 2-5A System in Human Immunodeficiency Virus-1-Infected CEM Cells by Propentofylline

Leuck

Kuusksalu

Kelve

et al. 1996

Antivir Chem Chemother

View full text Add to dashboard Cite

2′,5′-OIigoadenylates (2-5A) play an essential role in the establishment of the antiviral state of cells exposed to virus infection. However, - after an initial increase observed in some cell lines - the activity of the interferon (IFN)-inducible, 2-5A-forming 2′,5′-oligoadenylate synthetase (2-5A synthetase) strongly decreases soon after infection of cells with the human immunodeficiency virus-1 (HIV-1). In the present report, we show that in IFN-treated human T lymphoblastoid CEM cells, the decrease in 2-5A synthetase activity had already occurred at day 1 post infection (p.i.)- At days 3 and 5 p.i., the 2-5A synthetase activity in the IFN-treated infected cells amounted to only 10-12% of that in IFN-treated uninfected control cells. The decrease in 2-5A synthetase activity was accompanied by a decrease in 2-5A synthetase mRNA and protein. We found that the decrease in 2-5A synthetase activity can be retarded by addition of the cAMP phosphodiesterase inhibitor, propentofylline. At a concentration of 30-100 μM, propentofylline displayed a significant cytoprotective and antiviral effect on HIV-1-infected CEM cells.

show abstract

“…На ми знай де но подібності у змінах рівня IFN та ак тив ності 2',5'-ОАS за умов опроміне ння тва рин різни ми до за ми: в об ох орга нах мак си маль ний вміст ци токіну спос теріга ли після дії радіації в дозі 0,5 Гр, [22,23].…”

unclassified

Activity of 2',5'-oligoadenylate synthetase and interferon level in lymphocytes of rats exposed to radiation

Lavrova

Kompanets

2012

Biopolym. Cell

View full text Add to dashboard Cite

Aim. To determine 2',5'-oligoadenylate synthetase (2',5'-OAS) activity and interferon (IFN) level in lymphocytes of rats irradiated with 0.25, 0.5, 0.75 and 1.0 Gy doses, as well as to study the effect of interferon inducers on these parameters. Methods. Micro method of IFN titer determination by antiviral activity testing and spectrophotometric method of 2',5'-OAS activity determination were used. Results. An increase in IFN titer in lymphocytes of rats after irradiation with 0.25 and 0.5 Gy doses was shown. Higher radiation doses of 0.75 and 1.0 Gy caused a decrease of this parameter. The 2',5'-OAS activity exceeded a control at all applied doses, the maximum level in splenocytes corresponded to 0.25 Gy dose whereas the highest values in thymocytes were revealed at 0.5-1.0 Gy doses. The IFN inducers stimulated cytokine synthesis and increased the enzyme activity in lymphocytes of irradiated rats. Conclusions. The increase of 2',5'-OAS activity and IFN titer in lymphocytes of irradiated animals may be regarded as a protective post radiation reaction of cells. Under irradiation with higher doses – 0.75 and 1.0 Gy – the studied parameters decreased, that may be associated with more serious damage of cells, for correction of which the resources of repairing systems are not enough. The increased 2',5'-OAS activity and IFN titer in lymphocytes after their pre-incubation with IFN inducers can be considered as intensification of cellular protective postradiation mechanisms

show abstract

Oligoadenylate and Cyclic AMP: Interrelation and Mutual Regulation

Cited by 7 publications

References 40 publications

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

The 2–5 A system: Modulation of viral and cellular processes through acceleration of RNA degradation

Modulation of the Antiviral 2-5A System in Human Immunodeficiency Virus-1-Infected CEM Cells by Propentofylline

Activity of 2',5'-oligoadenylate synthetase and interferon level in lymphocytes of rats exposed to radiation

Contact Info

Product

Resources

About