Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 27-fold increase in 2',5'-oligoadenylate synthetase activity, an enzyme associated with the antiproliferative actions of interferon (IFN), was observed after treatment of HL-60 human leukemia cells with dimethyl sulfoxide (DMSO), an inducer of granulocytic differentiation of the cells. Enzyme activity was elevated after 24 h of exposure to DMSO, was maximal at 48 hours, and declined thereafter. A comparable increase was observed after treatment with 1 U of alpha interferon (IFN-alpha) per ml or 8 U of beta interferon (IFN-beta) per ml. Elevated levels of expression of other IFN-inducible genes, including type I histocompatibility antigen (HLA-B) mRNA and 2',5'-oligoadenylate phosphodiesterase activity, were also observed with DMSO treatment. DMSO-treated HL-60 cells had an increased amount of a 1.8-kilobase mRNA for oligoadenylate [oligo(A)] synthetase when compared with that of control cells; both DMSO- and IFN-treated HL-60 cells also expressed 1.6-, 3.4-, and 4.3-kilobase mRNA. The increase in both oligo(A) synthetase activity and mRNA levels was inhibited by polyclonal antiserum to human IFN-alpha; however, no IFN-alpha mRNA could be detected in the cells. Antiserum to IFN-beta or gamma interferon (IFN-gamma) had no effect on oligo(A) synthetase expression or activity nor was there any detectable IFN-beta 1 or IFN-beta 2 mRNA in the cells. The anti-IFN-alpha serum did not block the elevation of HLA-B mRNA in DMSO-treated cells. These observations suggest that the increased expression of oligo(A) synthetase in DMSO-treated cells may be mediated by the release of an IFN-alpha-like factor; however, the levels of any IFN-alpha mRNA produced in the cells were extremely low.
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PMID:Activation of 2',5'-oligoadenylate synthetase activity on induction of HL-60 leukemia cell differentiation. 247 65

The hallmark of "beta 2-interferon (IFN-beta 2)/hepatocyte-stimulating factor/interleukin 6" gene expression is its inducibility in different types of human cells (fibroblasts, monocytes, epithelial cells, and endothelial cells) by different stimuli, which include cytokines such as tumor necrosis factor, interleukin 1 (IL-1) and platelet-derived growth factor, different viruses, and bacterial products such as endotoxin. The activation by cytokines, viruses, and second messenger agonists of the IFN-beta 2 promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene was studied after transfection into HeLa cells. A chimeric gene containing IFN-beta 2 DNA from -1180 to +13 linked to the CAT gene was inducible approximately 10-fold by phorbol 12-myristate 13-acetate (PMA), followed, in decreasing order, by pseudorabies and Sendai viruses (7- to 11-fold each); serum (6- to 9-fold); the cytokines tumor necrosis factor, IL-1, and epidermal growth factor (3- to 5-fold each); the cAMP agonists BrcAMP and forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (2- to 6-fold each); poly(I).poly(C) (2- to 4-fold); 1,2-diacylglycerol and the calcium ionophore A23187 (1.5- to 2-fold each). Bacterial endotoxin did not activate this IFN-beta 2/CAT fusion gene in HeLa cells. Deletion of the 5' boundary of the IFN-beta 2 DNA from -1180 to -596 in the fusion gene preserved its activation by IL-1, tumor necrosis factor, epidermal growth factor, serum, pseudorabies, and Sendai viruses and by PMA, Br-cAMP, and forskolin; deletion to -225 led to a small reduction (by a factor of 1.5-2) in the responsiveness to serum, PMA, and Sendai virus but not to the other inducers; a further deletion to -112 greatly reduced all responsiveness. Thus, the region between -225 and -113 in IFN-beta 2, which contains DNA motifs similar to the regulatory elements in the human c-fos gene, appears to contain the major cis-acting regulatory elements responsible for the activation of the IFN-beta 2 promoter by several different cytokines, viruses, and second messenger agonists.
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PMID:Activation of the human "beta 2-interferon/hepatocyte-stimulating factor/interleukin 6" promoter by cytokines, viruses, and second messenger agonists. 304 22

The antiproliferative effect of human fibroblast interferon (IFN-beta), human recombinant leukocyte interferon (IFN-alpha A), and polyinosinic . polycytidylic acid [poly(I) . poly(C)] was investigated in human colon carcinoma cell line HT-29. Exposure of HT-29 cells for 1 to 3 days with 100 to 2000 units of either interferon preparation resulted in a 30 to 50% inhibition of growth after 3 days. Similar treatment of cells with 100 micrograms per ml poly(I) . poly(C) resulted in progressive inhibition of growth by 50 to 60% in 2 to 3 days. The inhibitory effects of combination of either IFN-beta or IFN-alpha A with poly(I) . poly(C) were additive with up to 80 to 90% inhibition of cell growth after 3 days of exposure. None of the treatment regimens was markedly cytocidal, and only 25 to 30% reduction in colony formation was noted under optimal treatment conditions following 2 to 3 days of drug exposure. Measurements of DNA, RNA, and protein synthesis following interferon treatment indicated a dose-dependent reduction in all three parameters, particularly when interferon was administered with poly(I) . poly(C). The associated changes in the (2',5')oligoadenylate [(2',5')oligo(A)] pathway produced by IFN-beta and IFL-alpha A were measured under growth-inhibitory conditions. A concentration-dependent induction of (2',5')oligo(A) synthetase was produced by IFN-beta or IFL-alpha A with a concomitant decrease in (2',5')oligo(A) phosphodiesterase. Poly(I) . poly(C) alone induced (2',5')oligo(A) synthetase activity but had no effect on the associated activity of phosphodiesterase. The combination of either IFN-beta or IFL-alpha A and poly(I) . poly(C) further reduced (2',5')oligo(A) phosphodiesterase activity. There was no general dose-response correlation between the induction of (2',5')oligo(A) synthetase and the cytostatic activity of interferon treatment alone or in combination with double-stranded RNA.
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PMID:Effects of fibroblast and recombinant leukocyte interferons and double-stranded RNA on ppp(2'-5')An synthesis and cell proliferation in human colon carcinoma cells in vitro. 618 84