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)

Ca2+, Mg2+ dependent endonuclease activity of isolated nuclei from rat liver disappeared completely within one to two hours after intraperitoneal administration of inhibitors of eukaryotic protein synthesis such as cycloheximide or puromycin. Actinomycin D, on the other hand, revealed no inhibition of the endonuclease activity, but even reversed the effect of cycloheximide by simultaneous addition.
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PMID:Rapid inactivation of Ca2+, Mg2+-dependent endonuclease of rat liver nuclei after cycloheximide treatment. 671 46

DNA fragmentation and nuclear condensation are key features in the regulated cell death of higher animal cells. Nuclear death also occurs as part of a developmentally programmed process during the sexual life cycle of the unicellular organism Tetrahymena. We examined the regulation of nuclear death and the relationship between DNA fragmentation and chromatin condensation in this model system. Nuclear death is accompanied by DNA digestion to low-molecular-weight oligonucleosomal-length fragments, in agreement with a previous study, indicating an endonuclease-like activity typical of apoptosis in higher organisms. Actinomycin D and cycloheximide block DNA digestion as well as nuclear condensation suggesting that nuclear death is under genetic regulation. DNA digestion is completely blocked by aurin, a general nuclease inhibitor. In addition, when DNA fragmentation is blocked, nuclear condensation also fails to occur. Moreover, a kinetic analysis of DNA breakdown, using agarose gels, shows that some DNA digestion occurs before nuclear condensation has taken place. Thus the initiation of DNA digestion may provide conditions necessary for nuclear condensation. Temporary inhibition of nuclear death aborts the death program since after removal of inhibitors cells revert to a vegetative pathway without having eliminated the old or developed the new macronucleus. Zn2+ and EGTA, both of which inhibit apoptosis in some cell types, fail to prevent nuclear condensation or DNA digestion in Tetrahymena, suggesting a requirement here for an endonuclease which is Ca2+-independent and Zn2+-insensitive. With the TUNEL assay, DNA breakdown is detected exclusively in the condensed macronucleus (and occasional micronuclei identified as degenerating haploid products of meiosis), but not in precondensed macronuclei. These studies show that apoptotic-like DNA fragmentation occurs after condensation of the degenerating macronucleus. However, early DNA digestion may be critical for nuclear condensation and subsequent degeneration.
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PMID:DNA digestion and chromatin condensation during nuclear death in Tetrahymena. 866 Sep 24

We have previously demonstrated that cisplatin-induced nephrotoxicity is associated with the induction of apoptosis using mouse renal cells derived from the terminal proximal tubule (S3) which is the major target site of cisplatin-induced injury. The purpose of this study was to elucidate the intracellular mechanisms leading to the cisplatin-induced apoptosis of S3 cells. Actinomycin D (an inhibitor of RNA synthesis), cycloheximide (an inhibitor of protein synthesis) and aurintricarboxylic acid (an endonuclease inhibitor) reduced the extent of DNA fragmentation, a biochemical parameter of apoptosis, in cisplatin-treated S3 cells. Furthermore, cisplatin-induced apoptosis of S3 cells was accompanied by an increase in the level of c-fos mRNA expression, which is inhibited by pretreatment of the cells with actinomycin D, but not with cycloheximide or aurintricarboxylic acid. In contrast, outer medullary collecting duct cells treated with cisplatin exhibited morphological changes characteristic of apoptosis and an increase in the level of c-fos mRNA expression, but no increase in the extent of DNA fragmentation. In conclusion, the synthesis of macromolecules such as RNA and protein, endonuclease activation and c-fos expression appear to be involved in the intracellular pathways leading to the induction of apoptosis in cisplatin-treated S3 cells. In addition, the response to cisplatin may be different in different cells.
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PMID:Involvement of macromolecule synthesis, endonuclease activation and c-fos expression in cisplatin-induced apoptosis of mouse proximal tubule cells. 957 5