Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to determine whether specific interactions between cAMP and glucocorticoids regulate apoptosis in thymocytes. Incubation of murine thymocytes with agents that elevate the cAMP level resulted in enhancement of glucocorticoid-induced Ca2+ increases, DNA fragmentation, and cell death compared to levels observed in thymocytes treated with steroid alone. cAMP did not affect DNA fragmentation in thymocytes treated with Ca2+ ionophore, a compound that induces endonuclease activation via an independent mechanism. Treatment with cAMP also increased glucocorticoid potency by lowering the concentration of steroid required for induction of apoptosis. The mechanism of cAMP action appeared to involve the glucocorticoid receptor, since the glucocorticoid antagonist RU-486 abrogated the cAMP response in animals treated with the adenosine analog NECA in vivo. Analysis of cellular glucocorticoid binding and receptor protein levels revealed modest cAMP-stimulated increases that appeared insufficient to account for the effects of cAMP on endogenous endonuclease activation, suggesting the possible involvement of a posttranslational mechanism in the response. These results demonstrate that cAMP and glucocorticoids synergize to promote apoptosis in thymocytes via a mechanism that appears to involve modification of glucocorticoid receptor activity.
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PMID:Cyclic AMP potentiates glucocorticoid-induced endogenous endonuclease activation in thymocytes. 838 20

One of the main effects of various stress factors, including ionizing radiation, is DNA damage. Accumulation of DNA damage and somatic mutations in the somatic tissues is regarded as one of the basic mechanisms of aging. We have developed an approach to the study of molecular and genetic mechanisms of radioadaptation, which is based on the analysis of changes in the lifespan of Drosophila with a transformed genotype. In this study we investigated the radioadaptive response and hormesis by radiation-induced changed of the lifespan of different strains of Drosophila melanogaster, such as a wild type strain Canton-Sand strains with mutations in DNA damage response gene (homologue of GADD45), excision repair genes (homologues of XPF, XPC, PCNA) and double-strand breaks repair genes (homologues of RAD54, XRCC3, BLM). The exposure to irradiation at the dose rate of 40 cGy was performed chronically through the stages of fly development; an acute exposure at the dose rate of 30 Gy was applied to the adult stages of flies. Also, we investigated the resistance to acute gamma-radiation of Drosophila with conditional ubiquitous overexpression of genes that are involved in DNA damage recognition (homologues of GADD45, HUS1, CHK2), excision repair (homologues of XPF, XPC, AP-endonuclease-1) and double-strand break repair (homologues of BRCA2, XRCC3, KU80, WRNexo). In the wild type strain Canton-S, manifestation of the radioadaptive response and radiation hormesis were observed. In individuals with DNA repair gene mutations, no radioadaptive response was observed, or observed to a lesser extent than in wild type flies. Mifepristone--inducible transgene activation does not lead to an increase in resistance to acute irradiation by the parameters of lifespan of Drosophila. Overexpression of DNA repair genes led to a sharp decline in lifespan also in the absence of irradiation.
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PMID:[Role of DNA repair genes in radiation-induced changes of lifespan of Drosophila melanogaster]. 2577 40