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)

Metabotropic glutamate receptor (mGluR) activation prevents neurodegeneration against nitric oxide (NO)-induced programmed cell death (PCD). We therefore investigated whether specific neuronal endogenous deoxyribonucleases, enzymes recently identified to be responsible for the maintenance of DNA integrity, mediated mGluR protection against NO. In rat primary hippocampal neurons, injury was assessed by using a 0.4% trypan blue dye exclusion method and TUNEL assay 24 h following treatment with the NO generators sodium nitroprusside (300 microM) or SIN-1 (300 microM). DNA digestion studies using neuronal cell extracts were employed to assess specific endonuclease activity. Individual application of aurintricarboxylic acid (ATA) (10 microM), an endonuclease inhibitor, or the mGluR agonists 1S,3R-ACPD (750 microM), DHPG (750 microM), L-CCG-I (750 microM), or L-AP4 (750 microM) prior to NO exposure significantly increased neuronal survival. Yet, combination therapy with ATA (10 microM) and the mGluR agonists did not synergistically improve neuronal survival, suggesting a common pathway of protection for ATA and the mGluRs that is dependent upon the modulation of neuronal endonuclease activity. In further support of this premise, protection by the mGluR agonists 1S,3R-ACPD, DHPG, L-CCG-I, and L-AP4 was significantly decreased during enhancement of endonuclease activity with the zinc chelator, N,N,N',N',-tetrakis (2-pyridylmethyl) ethylenediamine. Antagonism of the mGluR system was ineffective against endonuclease induced DNA destruction. Further assessment with DNA digestion assays identified two distinct mechanisms to maintain DNA integrity, a Ca2+/Mg2+-dependent endonuclease inhibited by L-AP4 and a magnesium dependent endonuclease inhibited by 1S,3R-ACPD. These neuroprotective mechanisms during activation of the mGluR system were also intricately linked to the active reversal of the biphasic intracellular pH changes induced by NO. Further investigation into the molecular pathways modulated by mGluRs may identify specific mechanisms that can maintain DNA integrity during adverse cellular environments.
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PMID:Metabotropic glutamate receptors prevent programmed cell death through the modulation of neuronal endonuclease activity and intracellular pH. 991 7

Clostridium difficile is now recognized as the major agent responsible for nosocomial diarrhea in adults. Among the genotyping methods available, arbitrarily primed PCR (AP-PCR), PCR-ribotyping, and pulsed-field gel electrophoresis (PFGE) have been widely used for investigating outbreaks of C. difficile infections. However, the comparative typing ability, reproducibility, discriminatory power, and efficiency of these methods have not been fully investigated. We compared the results of three methods-AP-PCR with three different primers (AP3, AP4, and AP5), PCR-ribotyping, and PFGE (with SmaI endonuclease)-to differentiate 99 strains of C. difficile that had been previously serogrouped. Typing abilities were 100% for PCR-ribotyping and AP-PCR with AP3 and 90% for PFGE, due to early DNA degradation in strains from serogroup G. Reproducibilities were 100% for PCR-ribotyping and PFGE but only 88% for AP-PCR with AP3, 67% for AP-PCR with AP4, and 33% for AP-PCR with AP5. Discriminatory power for unrelated strains was >0.95 for all the methods but was lower for PCR-ribotyping among serogroups D and C. PCR-based methods were easier and quicker to perform, but their fingerprints were more difficult to interpret than those of PFGE. We conclude that PCR-ribotyping offers the best combination of advantages as an initial typing tool for C. difficile.
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PMID:Comparison of PCR-ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis for typing Clostridium difficile. 1087 30

The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein involved in repair of oxidative DNA damage as well as in transcriptional regulation, is often overexpressed in tumor cells. APE1 was earlier shown to stimulate p53's DNA binding and its transactivation function in the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) gene. Here, we show APE1's stable binding to p53 cis elements which are required for p53-mediated activation of p21 in p53-expressing wild type HCT116 cells. However, surprisingly, we observed APE1-dependent repression of p21 in isogenic p53-null HCT116 cells. Ectopic expression of p53 in the p53-null cells abrogated this repression suggesting that APE1's negative regulatory role in p21 expression is dependent on the p53 status. We then identified APE1's another binding site in p21's proximal promoter region containing cis elements for AP4, a repressor of p21. Interestingly, APE1 and AP4 showed mutual dependence for p21 repression. Moreover, ectopic p53 in p53-null cells inhibited AP4's association with APE1, their binding to the promoter and p21 repression. These results together establish APE1's role as a co-activator or co-repressor of p21 gene, dependent on p53 status. It is thus likely that APE1 overexpression and inactivation of p53, often observed in tumor cells, promote tumor cell proliferation by constitutively downregulating p21 expression.
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PMID:Dual regulatory roles of human AP-endonuclease (APE1/Ref-1) in CDKN1A/p21 expression. 2387 36