Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysates of Moloney murine sarcoma-leukemia virus [M-MSV(MLV)], a virus complex grown in the rat cell line 78A-1, were found to contain three RNase H species separable by polycytidylic acid[poly(C)]-agarose chromatography. RNase H activity (RNase H I) associated with RNA-directed DNA polymerase eluted at 0.23 M KCI from poly(C)-agarose. RNase H II, which eluted from poly(C)-agarose at 0.12 M KCI and was not associated with DNA polymerase activity, was shown to be identical to an RNase H species (designated RNase H II) previously isolated from M-MSV(MLV) by a different procedure (G. F. Gerard and D. P. Grandgenett, J. Virol. 15:785-797, 1975). M-MSV(MLV) RNase H II was established to be a random exohybridase that requires free-chain termini in its hybrid substrate for activity. Lysates of Rickard feline leukemia virus also contained RNase H activity not associated with DNA polymerase activity that eluted from poly(C)-agarose at 0.12 M KCl. A third species of enzyme from M-MSV(MLV) lysates, called RNase H III, did not bind to poly(C)-agarose in 0.06 M KCl. RNase H III was purified from lysates of M-MSV(MLV) and M-MLV (grown in mouse cells) by sequential chromatography on poly(C)-agarose, DEAE-cellulose, phosphocellulose, and polyuridylic acid-Sepharose. Purified RNase H III (i) was free of any associated DNA polymerase activity, (ii) had an apparent molecular weight of 30,000 determined by Sephadex G-100 gel filtration, (iii) had an absolute requirement for Mn2+ (1 mM optimum) for the degradation of [3H](A)n.(dT)n, (iv) was inhibited by the presence of any salt in reaction mixtures, and (v) was endoribonucleolytic in its mode of action as indicated by the size distribution of limited degradation products of [3H](A)n.(dT)n. RNase H III was inhibited by antisera prepared against Rauscher MLV and simian sarcoma virus reverse transcriptase, and the quantity of RNase H III and RNase H I present in lysates of M-MLV were reduced and increased proportionately if virus was lysed in the presence of the protease inhibitor phenylmethylsulfonyl fluoride. These results indicate that RNase H III is a proteolytic cleavage product of DNA polymerase-RNase H. Substantial RNase H activity that did not bind to poly(C)-agarose in 0.06 M KCl was also found in lysates of Harvey MSV(MLV), Rauscher MLV, and Rickard feline leukemia virus, but not in lysates of avian myeloblastosis virus.
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PMID:Multiple RNase H activities in mammalian type C retravirus lysates. 7 33

The synthesis and processing of feline leukemia virus (FeLV) polypeptides were studied in a chronically infected feline thymus tumor cell line, F-422, which produces the Rickard strain of FeLV. Immune precipitation with antiserum to FeLV p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to isolate intracellular FeLV p30 and possible precursor polypeptides. SDS-PAGE of immune precipitates from cells pulse-labeled for 2.5 min with [35S]methionin revealed the presence of a 60,000-dalton precursor polypeptide (Pp60) as well as a 30,000-dalton polypeptide. When cells were grown in the presence of the proline analogue L-azetidine-2-carboxylic acid, a 70,000-dalton precursor polypeptide (Pp70) was found in addition to Pp60 after a 2.5-min pulse. The cleavage of Pp60 could be partially inhibited by the general protease inhibitor phenyl methyl sulfonyl fluoride (PMSF). This partial inhibition was found to occur only if PMSF was present during pulse-labeling. Intracellular Pp70 and Pp60 and FeLV virion p70, p30, p15, p11, and p10 were subjected to tryptic peptide analysis. The results of this tryptic peptide analysis demonstrated that intracellular Pp70 and virion p70 were identical and that both contained the tryptic peptides of FeLV p30, p15, p11, and p10. Pp60 contained the tryptic peptides of FeLV P30, P15, and P10, but lacked the tryptic peptides of P11. The results of pactamycin gene ordering experiments indicated that the small structural proteins of FeLV are ordered p11-p15-p10-p30. The data indicate that the small structural proteins of FeLV are synthesized as part of a 70,000-dalton precursor. A cleavage scheme for the generation of FeLV p70, p30, p15, p11, and p10 from precursor polypeptides is proposed.
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PMID:Analysis of intracellular feline leukemia virus proteins II. Generation of feline leukemia virus structural proteins from precursor polypeptides. 19 17

Serum samples from 564 Caucasian patients suffering from either leukaemia or lymphoma were typed for the protease inhibitor (Pi) alpha-1-antitrypsin (AAT). No evidence was found for the predisposition of any Pi phenotype to leukaemia or lymphoma. However, the frequency of PiM3 was significantly lowered among patients with acute myeloid leukaemia.
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PMID:Alpha-1-antitrypsin phenotypes in leukaemia and lymphoma. 238 27

Membrane dynamics of human leukemia and lymphoma cell lines were analyzed by investigating the effect of pH on fluorescence polarization (P) of the lipophilic probe diphenylhexatriene (DPH). The degree of P varied as a function of pH, depending on the cell lines. These variations were not detected in phospholipid vesicles. In addition, they were prevented by treatments with glutaraldehyde, sodium azide or phenylmethylsulfanyl fluoride, a specific protease inhibitor. Therefore, these P value changes might be influenced by protein modification.
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PMID:Membrane dynamics in human leukemia and lymphoma cells. pH dependency of diphenylhexatriene fluorescence polarization. 687 77

Two approaches have been used to assess the hypothesis that granzymes secreted by cytotoxic lymphocytes act within the target cells to trigger an internal disintegration pathway leading to target cell lysis. The lytic properties of several clones of rat basophilic leukemia cells transfected with either cytolysin (perforin) alone (RBL-cy) or a combination of cytolysin and granzyme A (RBL-cy-gza) were compared with cloned CTL. Analysis of the kinetics of target cell 125I-DNA vs 51Cr release with three tumor targets showed negligible DNA release with RBL-cy, less extensive 125I-DNA release relative to 51Cr release with RBL-cy-gza effector cells, whereas CTL caused greater or equal DNA release than 51Cr release at all time points. Using three different tumor target cells, comparison of RBL-cy-gza and RBL-cy clones in multiple experiments shows that RBL-cy-gza are on average more than threefold more lytic than RBL-cy. This distinction was not seen with red cell targets, in which an internal disintegration pathway does not operate. A second approach to this issue consisted of cytoplasmic loading of tumor target cells with aprotinin, a macromolecular protease inhibitor known to inhibit granzyme A and probably other granzymes. Although the control BSA-loaded target cells were essentially identical to nonloaded targets in all cases, aprotinin-loaded targets showed substantially lower release of both 51Cr and 125I-DNA with both CTL and RBL-cy-gza effector cells. In contrast, aprotinin-loaded targets were lysed with the same efficiency as control targets by RBL-cy effector cells. We conclude that secreted granzymes contribute to target lysis by triggering a target cell internal disintegration pathway that leads to both lysis and DNA breakdown.
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PMID:Cytotoxic lymphocyte granzymes trigger a target cell internal disintegration pathway leading to cytolysis and DNA breakdown. 750 56

Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polypeptides in cultures of human T lymphocytes infected with human immunodeficiency virus type 1 (HIV-1) and therefore suppress the infectivity of HIV-1 in vitro. We have previously reported the antiviral activity in vitro of HIV-1 protease inhibitors against the C-type retrovirus Rauscher murine leukemia virus (RMuLV) and the lentivirus simian immunodeficiency virus (SIV). The same compounds which blocked the infectivity of HIV-1 also inhibited the infectivity of RMuLV and SIV in vitro. This report extends these findings by testing the antiviral activity of HIV-1 protease inhibitors in vivo in the RMuLV model. RMuLV-infected mice were treated twice a day (bid) with either an active (SKF 108922) or inactive (SKF 109273) compound for fourteen days by the intraperitoneal (i.p.) route. Compared with excipient control, SKF 108922, formulated with hydroxypropyl-beta-cyclodextrin (HPB), reduced virus-induced splenomegaly, viremia, and serum reverse transcriptase (RT) levels, while SKF 109273 was inactive. The HPB vehicle by itself enhanced replication of RMuLV. The effects of changing the formulation and the route of administration were examined. SKF 108922, formulated in HPB, had similar antiviral activity when administered by the i.p. or subcutaneous (SC) routes. However, SKF 108922 administered as a colloidal suspension in cholesterol sulfate (CS) had no detectable antiviral effect. Measurements of the circulating levels of the protease inhibitor in plasma explained this result. Plasma concentrations of SKF 108922 exceeded 1000 nM within 10 min after SC administration of the compound solubilized in HPB, but SKF 108922 was not detected in plasma after SC administration of the same dose formulated with CS. Information on optimal conditions for administering these agents should prove useful in guiding their clinical application Therefore, RMuLV should provide a good model for the preclinical evaluation and development of this class of agents for the treatment of HIV.
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PMID:Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in mice. 873 97

Many anticancer agents induce apoptosis in human leukemia cells. Among the various leukemia cells, especially HL-60 cells and U937 cells are very sensitive to apoptosis upon anticancer agents treatment. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage in human myeloid leukemia HL-60 and U937 cells. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on anticancer agent-induced internucleosomal DNA cleavage. Our data indicate that serine and ICE-like proteases may be involved in anticancer agent-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in human myeloid leukemia HL-60 and U937 cells.
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PMID:[The mechanism of apoptosis induced by anticancer agents in human leukemia cells]. 874 73

The present study was designed to investigate the contribution of proteases in anticancer agents-induced apoptosis of human leukemia HL-60 cells. A serine protease inhibitor TPCK and an ICE-like protease inhibitor VAD-FMK prevented etoposide, camptothecin and ara-C-induced internucleosomal DNA cleavage. Using a cell-free system, we have examined the inhibitory mechanism of these inhibitors on etoposide-induced internucleosomal DNA cleavage. We found that cell lysates prepared from etoposide-treated HL-60 cells undergoing apoptosis contain the significant activity to induce internucleosomal DNA fragmentation in isolated nuclei. On the other hand, we could not detect such activity in the cell lysates from untreated HL-60 cells. Treatment of the cell lysates with a serine protease inhibitor TPCK abrogated the DNA fragmenting activity. An ICE-like protease inhibitor VAD-FMK had no effect on this DNA fragmenting activity in vitro. However, the formation of TPCK-sensitive DNA fragmenting activity in etoposide-treated cells was blocked by the VAD-FMK. These data indicate that serine and ICE-like proteases may be involved in etoposide-induced apoptosis at the different stages, and especially a serine protease may be closely associated with the final step for induction of DNA fragmentation during apoptosis in HL-60 cells.
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PMID:[The mechanism of apoptosis induced by anticancer agents in human leukemia HL-60 cells]. 877 71

The generation of ceramides by the action of acidic and/or neutral sphingomyelinases has been implicated in many forms of apoptosis. We investigated whether exposure to ceramides is sufficient to induce apoptosis in human leukemia cells and, if so, what the characteristics of this form of apoptosis might be. Treatment of the acute lymphoblastic T-cell line CEM-C7H2 with short- and medium-chain ceramide analogs (C2-, C6-, and C8-ceramide) resulted in apoptosis, whereas the inactive C2-dihydroceramide had no effect on cell survival. Induction of apoptosis was relatively slow (approximately 40% after 24 h) and required high concentrations of ceramide analogs (40-100 microM). To investigate a possible involvement of interleukin 1-beta-converting enzyme (ICE) or ICE-related proteases, we treated CEM-C7H2 sublines constitutively expressing the vaccinia virus protease inhibitor crmA with ceramide analogs. Although such cells were completely resistant to apoptosis induced by antibodies to the Apo-1/Fas surface receptor (a form of apoptosis known to be inhibitable by CrmA), they were not protected from ceramide-induced cell death. In contrast, tetracycline-regulated overexpression of Bcl-2 protected CEM-C7H2 sublines stably transfected with corresponding constructs from ceramide-induced apoptosis. Thus, in these human leukemia cells, ceramides induce a relatively slow death response that can be prevented by Bcl-2, but is independent of CrmA-inhibitable proteases. These characteristics distinguish ceramide-induced from other forms of apoptosis, such as Apo-1/Fas-induced cell death where ceramide production has been causally implicated.
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PMID:Ceramides induce a form of apoptosis in human acute lymphoblastic leukemia cells that is inhibited by Bcl-2, but not by CrmA. 900 May 5

The biochemical mechanism(s) by which germ cells can form specialized junctions with Sertoli cells in the seminiferous epithelium at various stages of the spermatogenic cycle is unknown. This study sought to examine the biochemical changes that are involved when germ cells are cocultured with Sertoli cells in vitro preceding the establishment of specialized Sertoli-germ cell junctions. While isolated germ cells were allowed to attach to Sertoli cells, media from both the apical and basal compartments of bicameral units were collected to assess serine and cysteine protease activity. The expression of selected serine and cysteine proteases and their corresponding inhibitors in these Sertoli-germ cell cocultures was also examined by RT-PCR. Using an [125I]-collagen film assay, a transient but significant increase in serine protease activity was noted in both the apical and basal compartments when germ cells began to settle onto the Sertoli cell monolayer preceding the formation of intercellular junctions. A specific tryptase (RNK-Tryp 2, a serine protease formerly cloned from a rat granular lymphocyte leukemia cell line, RNK-16, cDNA expression library) was shown to be expressed exclusively by Sertoli cells and not germ cells. Furthermore, Sertoli cell tryptase expression as well as urokinase plasminogen activator (u-PA, also a serine protease) increased significantly when germ cells were adhering to Sertoli cells. The decline in total serine protease activity when Sertoli-germ cell junctions were being formed was accompanied by a concomitant increase in alpha2-macroglobulin (alpha2-MG, a nonspecific protease inhibitor) expression. No significant changes in cysteine protease activity in either the apical or basal compartment were noted. However, there was a transient but significant increase in cathepsin L expression when germ cells were adhering to Sertoli cells preceding cell junction formation. The subsequent reduction in cathepsin L expression after this transient increase was accompanied by a concomitant increase in cystatin C expression. These results suggest that proteases and their corresponding inhibitors are working synergistically and are likely to be involved in the adherence of germ cells to Sertoli cells and the subsequent formation of intercellular junctions.
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PMID:Interactions of proteases and protease inhibitors in Sertoli-germ cell cocultures preceding the formation of specialized Sertoli-germ cell junctions in vitro. 943 34


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