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

Rapid and massive death of motoneurons occurs following axotomy in neonatal mammals. This likely results from the neurons being deprived of access to target-derived trophic factors, as their death can be prevented by application of a variety of neurotrophic factors to the proximal end of the cut nerve. Since trophic factor-deprived embryonic chick motoneurons undergo apoptosis in vitro, we have investigated whether axotomized neonatal rat facial motoneurons undergo apoptotic cell death in vivo. Following facial nerve transection during the first postnatal day, the dying motoneurons show characteristic morphological changes of apoptosis and undergo DNA fragmentation, as detected by an in situ end labeling technique. An initial sharp burst of DNA fragmentation, between 12 and 24 h postaxotomy, accompanies a steep decline in neuronal numbers, indicating that neuronal cell death rapidly follows endonuclease cleavage of DNA. However, the interval between axotomy and onset of DNA fragmentation varies widely. By 4 days postnatum only 38% of the lesioned motoneurons have survived an initial rapid phase of neuronal loss, whereas 11% survive to 10 days postnatum at least. NADPH-diaphorase/nitric oxide synthase activity has been implicated as having a causal role in the death of lesioned motoneurons. We have found that there is a sustained increase in the intensity of NADPH-diaphorase histochemical staining in axotomized neonatal facial motoneurons, but that this is first detectable well after the onset of DNA fragmentation and cell death. This suggests that nitric oxide, or its metabolites, does not initiate cell death in this model.
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PMID:Axotomy-induced apoptotic cell death of neonatal rat facial motoneurons: time course analysis and relation to NADPH-diaphorase activity. 859 94

We investigated whether murine peritoneal macrophages treated with cisplatin or interferon (IFN)-gamma alone, or in combination, could undergo apoptosis, and whether this results either from the cytotoxic effect of the activating agents or indirectly in an autocrine manner by the cytotoxic molecules released by them upon activation. Our data suggest that cisplatin, which has been shown to induce apoptosis in a number of normal as well as tumor cell types, did not induce apoptosis in murine peritoneal macrophages nor was apoptosis caused by IFN-gamma. However, combined treatment with cisplatin and IFN-gamma induced apoptosis in macrophages as studied by percent DNA fragmentation assay, qualitative analysis of DNA on agarose gel electrophoresis, and morphological and nuclear alterations studied by phase contrast and fluorescence microscopy. The factor responsible for inducing apoptosis in macrophages was found to be a higher concentration of NO produced by them upon activation with cisplatin and IFN-gamma. Macrophages treated with cisplatin or IFN-gamma alone produced a low level of NO and did not undergo apoptosis. The inhibitor of NO synthase, L-NMMA, prevented apoptosis in macrophages treated with cisplatin and IFN-gamma, suggesting the involvement of NO in the induction of apoptosis in macrophages. The role of NO in inducing apoptosis in macrophages was further confirmed by the observation that direct treatment with sodium nitroprusside, a NO donor, resulted in apoptosis in macrophages. We have also shown that NO-induced apoptosis in macrophages activated with cisplatin and IFN-gamma requires activation of an endonuclease, as the endonuclease inhibitor, aurine tricarboxylic acid, prevented apoptosis in them.
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PMID:Murine peritoneal macrophages treated with cisplatin and interferon-gamma undergo NO-mediated apoptosis via activation of an endonuclease. 963 24

We have analysed the effects of endogenously and exogenously generated nitric oxide (NO) in cultured mammalian fibroblasts on: (i) the steady-state (background) levels of oxidative DNA base modifications; (ii) the susceptibility of the cells to the induction of additional DNA damage and micronuclei by H(2)O(2); and (iii) the repair kinetics of various types of DNA modifications. Steady-state levels of oxidative DNA base modifications, measured by means of an alkaline elution assay in combination with the repair endonuclease Fpg protein, were similar in NO-overproducing B6 mouse fibroblasts stably transfected with an inducible NO synthase (iNOS) and in control cells. Increased oxidative damage was only observed after exposure to high (toxic) concentrations of exogenous NO generated by decomposition of dipropylenetriamine-NONOate (DPTA-NONOate). Under these conditions, the spectrum of DNA modifications was similar to that induced by 3-morpholinosydnonimine, which generates peroxynitrite. The repair rate of additional oxidative DNA base modifications induced by photosensitization was not affected by the endogenous NO generation in the iNOS-transfected cells. However, it was completely blocked after pre-treatment with DPTA-NONOate at concentrations that did not cause oxidative DNA damage by themselves. In contrast, the repair of DNA single-strand breaks, sites of base loss (AP sites) and UVB-induced pyrimidine photodimers, was not affected. The endogenous generation of NO in the iNOS-transfected fibroblasts was associated with a protection from DNA single-strand break formation and micronuclei induction by H(2)O(2). These results indicate that NO generates cellular DNA damage only inefficiently and can even protect from DNA damage by H(2)O(2), but it selectively inhibits the repair of oxidative DNA base modifications.
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PMID:Influence of nitric oxide on the generation and repair of oxidative DNA damage in mammalian cells. 1189 62

Redox factor-1 (Ref-1) is a ubiquitously expressed protein with proven roles as a modulator of redox-sensitive transcription, and as an endonuclease in the base excision repair pathway of oxidatively damaged DNA. Although Ref-1 is induced by a variety of oxidative stress and protects cells against oxidative stress, the function of Ref-1 in regulating nitric oxide (NO) synthesis has not been elucidated to date. We investigated the role of Ref-1 in regulating NO synthesis and NO-mediated apoptosis employing adenoviral-mediated overexpression of Ref-1 in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. LPS treatment produced NO synthesis and NO-mediated apoptosis. Forced overexpression of Ref-1 suppressed LPS-stimulated NO synthesis. In parallel with this, Ref-1 also mitigated alteration of inducible NO synthase expression and NO-mediated apoptosis. Our findings suggest that Ref-1 is implicated in protection against cell death resulting from oxidative stimuli containing NO.
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PMID:Overexpression of redox factor-1 negatively regulates NO synthesis and apoptosis in LPS-stimulated RAW 264.7 macrophages. 1470 22