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 molecular mechanism of cell death induced by 5-Fluoro-2'-deoxyuridine (FUdR) was investigated. FUdR caused cell death to induce dNTP pool imbalance and following DNA double strand breaks in mouse mammary tumor FM3A cells. We isolated a new endonuclease from FUdR-treated cells, named endonuclease S, that played an important role in FUdR-induced cell death. Cells treated with FUdR showed intracellular acidification before cell death formation. We observed that the endonuclease S in acidic cells may lead the DNA fragmentation. On the other hand, we observed that protease inhibitors (such as TLCK, TPCK, PMSF, p-APMSF, Pefabloc SC and Z-Asp-CH2-DCB) blocked intracellular acidification, DNA fragmentation and FUdR-induced cell death. But the inhibitors did not affect dNTP pool imbalance in the cells. These results suggest that proteases act at the point of downstream of dNTP pool imbalance and upstream of the intracellular acidification.
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PMID:The molecular mechanisms of 5-fluoro-2'-deoxyuridine induced cell death. 958 36

Cell death plays an essential role in cell homeostasis and the pathological process in cancer. Apoptosis has been identified by the internucleosomal DNA cleavage which appears to be associated with endonuclease activation. Proteolysis is considered to be an early event in apoptosis. We studied the effects of proteolysis on early apoptotic events, such as chromatin condensation, nuclear breakdown, DNA breakage and sensitivity to denaturation induced by anticancer drugs (camptothecin: CAM, 5-azacytidine: AZA) on HL-60 cells. CAM induced apoptosis on S phase and AZA on G1 phase. The internucleosomal DNA cleavage shown by both the presence of DNA fragments during gel electrophoresis and a large number of in situ DNA strands breaks (revealed in high intensity fluorescence FITC of cells in the TdT reaction) was prevented by the protease inhibitor, TPCK (N-tosyl-L-phenylalanine chlorometyl-ketone), as well as by an inhibitor of the apoptosis-associated endonuclease, ZnSO4. The protective effects were observed under conditions in which apoptosis was induced by agents with a different mechanism of action, such as the DNA damaging drug. CAM (topo-isomerase inhibitor), and an RNA antimetabolite, AZA. The protease inhibitor inhibits early events of apoptosis such as chromatin condensation, nuclear breakdown, DNA breakage and sensitivity to denaturation, which have different structures and a different mechanism of interaction with drugs. The results suggest that control of protease inhibitor may be a useful strategy to treat cancers.
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PMID:[Analysis of drug-induced apoptosis in human leukemic cell line (HL-60)]. 958 41

To examine the roles of a short form of p53 in the regulation of apoptosis in chicken lymphoblastoid tumor cell lines derived from Marek's disease (MD) and avian leukosis (AL), the expressions of the p53 proteins were analyzed in these cell lines in which apoptosis was chemically induced. In MSB1-O derived from MD, the expression of a 40 kDa protein of p53 was decreased and that of a 32 kDa protein, a short form of p53, was increased during apoptosis induced by actinomycin D. In 1104B1 derived from AL, the expressions of 42 and 32 kDa of p53 were increased during the apoptosis. The short form of p53 was undetectable in these cell lines when apoptosis was blocked by the pretreatment with endonuclease inhibitor, Zn2+, protease inhibitors, TPCK and TLCK, or caspase inhibitor, Z-VAD-FMK. In the transcriptional level, the expressions of bcl-2 and IAP were decreased in these cell lines during actinomycin D-induced apoptosis, but no change was detected in the expression level of p53. These results suggest that, in these chicken tumors, the short form of p53 could play a role in the initiation of apoptosis induced by the chemotherapeutic compound, and that the regulation of its expression may be important for the maintenance of transformation status.
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PMID:The presence of a short form of p53 in chicken lymphoblastoid cell lines during apoptosis. 1682 Jul 12