Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of pentoxifylline to lymphocytes caused a dose-dependent decrease in PHA-induced interleukin-2 receptor (IL-2R) expression. Expression of IL-2R protein and mRNA were inhibited by 60% at a concentration of 1 mM. Pentoxifylline also inhibited release of IL-2R into the medium by 85%. Treatment with recombinant IL-2 (50 U/ml) did not abrogate the effect of pentoxifylline. In addition to inhibition of IL-2R expression, pentoxifylline also decreased the expression of transferrin receptors and class I MHC antigens. Pentoxifylline also inhibited cell proliferation. However, aphidicolin, an inhibitor of DNA polymerase alpha inhibited cell proliferation to the same extent as pentoxifylline, but had no effect on IL-2R expression, indicating that inhibition of cell proliferation does not necessarily lead to inhibition of IL-2R expression. The inhibitory effect on IL-2R expression was also noted with other methylxanthines, theophylline and isobutylmethylxanthine, and with dbcAMP and forskolin. The inhibitory activity of pentoxifylline was prevented by W-13, a calmodulin antagonist, but not by HA-1004, a cyclic AMP-dependent protein kinase inhibitor. This suggests that pentoxifylline might act in part through a Ca2+/calmodulin-dependent mechanism. Pentoxifylline and other methylxanthines may prove useful in delineating the biochemical pathways involved in induction and expression of cell surface receptors.
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PMID:Pentoxifylline and other methyl xanthines inhibit interleukin-2 receptor expression in human lymphocytes. 170 25

We investigated whether DNA polymerase beta activity and expression in rat adrenal glands and testes are controlled by the cAMP dependent protein kinase (A-kinase) phosphorylation system in addition to anterior pituitary hormones. DNA polymerase beta mRNA expression in rat testes was decreased by hypophysectomy and recovered with administration of gonadotropic hormone, suggesting that this enzyme is controlled at the mRNA level by this pituitary hormone. In addition, DNA polymerase beta activity in the adrenal glands and testes and the amount of mRNA in the testes increased when cAMP was administered to the normal rat. This activity was decreased by administration of the cyclic AMP-dependent protein kinase inhibitor, H(8). Moreover, when alkaline phosphatase was added to the assay system in vitro, a decrease in DNA polymerase beta activity was observed. These findings indicate that changes in the activity and expression of DNA polymerase beta are mediated via cAMP and the A-kinase system, and that phosphorylation of this enzyme is also involved in this expression.
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PMID:Hormonal regulation of DNA polymerase beta activity and expression in rat adrenal glands and testes. 1208 74