Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary tyrosinemia type I is the most severe metabolic disease of the tyrosine catabolic pathway mainly affecting the liver. It is caused by deficiency of fumarylacetoacetate hydrolase, which prevents degradation of the toxic metabolite fumarylacetoacetate (FAA). We report here that FAA induces common effects (i.e., cell cycle arrest and apoptosis) in both human (HepG2) and rodent (Chinese hamster V79) cells, effects that seem to be temporally related. Both the antiproliferative and apoptosis-inducing activities of FAA are dose dependent and enhanced by glutathione (GSH) depletion with L-buthionine-(S,R)-sulfoximine (BSO). Short treatment (2 h) with 35 microM FAA/+BSO or 100 microM FAA/-BSO induced a transient cell cycle arrest at the G2/M transition (20% and 37%, respectively) 24 h post-treatment. In cells treated with 100 microM FAA/-BSO, an inactivation, followed by a rapid over-induction of cyclin B-dependent kinase occurred, which peaked 24 h post-treatment. Maximum levels of caspase-1 and caspase-3 activation were detected at 3 h and 32 h, respectively, whereas release of mitochondrial cytochrome c was maximal at 24-32 h post-treatment. The G2/M peak declined 24 h later, concomitantly with the appearance of a sub-G1, apoptotic population showing typical nucleosomal-sized DNA fragmentation and reduced mitochondrial transmembrane potential (Deltapsi(m)). These events were prevented by the general caspase inhibitor z-VAD-fmk, whereas G2/M arrest and subsequent apoptosis were abolished by GSH-monoethylester or N-acetylcysteine. Other tyrosine metabolites, maleylacetoacetate and succinylacetone, had no antiproliferative effects and induced only very low levels of apoptosis. These results suggest a modulator role of GSH in FAA-induced cell cycle disturbance and apoptosis where activation of cyclin B-dependent kinase and caspase-1 are early events preceding mitochondrial cytochrome c release, caspase-3 activation, and Deltapsi(m) loss. -Jorquera, R., Tanguay, R. M. Cyclin B-dependent kinase and caspase-1 activation precedes mitochondrial dysfunction in fumarylacetoacetate-induced apoptosis.
FASEB J 1999 Dec
PMID:Cyclin B-dependent kinase and caspase-1 activation precedes mitochondrial dysfunction in fumarylacetoacetate-induced apoptosis. 1059 76

Mechanisms that regulate conversion of prointerleukin-1beta (pro-IL-1beta) to its mature form by the cysteine protease caspase-1 are not well understood. In this study, we demonstrate that mature caspase-1 subunits are produced when human monocytes are treated with ATP and, like mature IL-1beta, are released extracellularly. Characterization of the pharmacological sensitivity of this stimulus-coupled response revealed that some caspase-1 inhibitors allow pro-IL-1beta secretion, whereas others do not. Two nonselective alkylating agents, N-ethylmaleimide and phenylarsine oxide, also blocked maturation and release of pro-IL-1beta. Two inhibitors of anion transport, glyburide and ethacrynic acid, blocked maturation of both caspase-1 and pro-IL-1beta and prevented release of the propolypeptides. Procaspase-3 was detected in monocyte extracts, but its proteolytic activation was not efficient in the presence of ATP. Maturation of procaspase-1 and release of the mature enzyme subunits therefore accompany stimulus-coupled human monocyte IL-1 post-translational processing. Agents that appear to selectively inhibit mature caspase-1 do not prevent ATP-treated cells from releasing their cytosolic components. On the other hand, anion transport inhibitors and alkylating agents arrest ATP-treated monocytes in a state where membrane latency is maintained. The data provided support the hypothesis that stimulus-coupled IL-1 post-translational processing involves a commitment to cell death.
J Biol Chem 1999 Dec 24
PMID:ATP treatment of human monocytes promotes caspase-1 maturation and externalization. 1060 Dec 48

Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4(+), CD8(+), CD45RA(+), and CD45RO(+)), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation.
J Exp Med 1999 Dec 20
PMID:Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells. 1060 47

The chromatographic performance of the Dionex IonPac ICE-AS6 ion exclusion column is investigated. Therefore, capacity factors, efficiency, peak symmetry, resolution, and selectivity are determined for various mono- and polyfunctional aliphatic carboxylic acids under selected chromatographic conditions. Except for the stronger acids (pKa1 < 3.75), the highest chromatographic efficiency is achieved at a column temperature of 40 or 50 degrees C, and peak shape is found to be optimal at approximately 60 degrees C. The separation of the stronger acids is favored by an eluent pH below 3.0 and column temperatures below 40 degrees C. The maximal effective plate numbers range between 126 (tartronic acid) and 6380 (4-oxovaleric acid). Hydroxy-substituted acids are less retained and less influenced by temperature changes than the unsubstituted compounds. It is estimated that size exclusion effects take part in the separation of aldonic acids. The addition of 1% isopropanol to the acidic eluent increases the chromatographic efficiency generally, whereas higher concentrations reduce the retention of several acids drastically.
J Chromatogr Sci 1999 Dec
PMID:Chromatographic properties of the ion-exclusion column IonPac ICE-AS6 and application in environmental analysis. Part I: Chromatographic properties. 1061 95

Previous in vitro studies showed that rat hypothalamic explants release interleukin-1beta (IL-1beta); such release is significantly increased by several stimuli including 56 mM KCl and NO-donors in 20-min experiments. Here we tested the hypothesis that the above stimuli act via a mechanism involving cleavage of the IL-1beta precursor by interleukin-1beta converting enzyme (ICE, also referred to as caspase-1). A cell-permeable form of the caspase-1 inhibitor I and two different stimuli, 56 mM KCl and sodium nitroprusside (SNP), were used. The inhibitor was able to counteract the increase in IL-1beta release induced by both K+ and SNP, while having no effect on basal release.
Neurosci Lett 1999 Dec 03
PMID:Depolarization and a NO-donor stimulate interleukin-1beta release from the rat hypothalamus via a mechanism involving caspase 1. 1062 6

Between April 1996 and May 1998, 20 consecutive patients with Ph chromosome-positive CML in first chronic phase without an HLA-identical sibling received the mini-ICE regimen shortly after diagnosis to mobilize progenitor cells into the peripheral blood (PBPCs). The sex distribution was 12 males and eight females and the median (range) age 48.5 (22-62) years. The time interval between diagnosis and mobilization was a median (range) of 2 (0-5) months. Leukaphereses were initiated during recovery from chemotherapy-induced aplasia. A median number of 3 (1-7) aphereses per patient were performed to collect >/=2.0 x 106 CD34+cells/kg. Cytogenetic analysis was performed on the aphereses products of 18 patients. Complete cytogenetic Ph chromosome negativity was observed in four patients, nine had a partial negativity, three a minimal negativity and two no negative cells. Southern blot for bcr-abl was negative in the remaining two patients but the polymerase chain reaction analysis was positive. Following reinfusion, severe neutropenia was present for a median of 8.5 (3-19) days and severe thrombocytopenia lasted a median of 8 (3-18) days. Ten patients did not develop febrile neutropenia with four of them being treated on an outpatient basis. Treatment-related mortality was not observed. In conclusion, our experience demonstrates the feasibility of mobilizing PBPCs shortly after the diagnosis of CML with a safe regimen. Of note, mini-ICE allowed the collection of apheresis products with at least a major component of Ph-negative cells in almost 75% of the patients.
Bone Marrow Transplant 1999 Dec
PMID:Mini-ICE regimen as mobilization therapy for chronic myelogenous leukaemia patients at diagnosis. 1062 36

Tanshinone II-A is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, a traditional herbal medicine that is known to induce antiinflammatory, anti-oxidative and cytotoxic activity. We have examined cellular effects of Tanshione II-A on HL60 human promyelocytic leukemic cells and K562 human erythroleukemic cells. Tanshione II-A induced a dose- and time-dependent DNA fragmentation into the multiples of 180 bp and specific proteolytic cleavage of poly(ADP-ribose) polymerase in both cell lines. PI-staining and flow cytometry analysis of K562 cells following Tanshione II-A treatment showed an increase of the cells possessing hypodiploid DNA indicative of apoptotic state of cells. Caspase-3 activity was significantly increased during Tanshinone II-A treatment of both HL60 and K562 cells, whereas caspase-1 activity was not changed. These results suggest that Tanshione II-A induced HL60 and K562 cellular apoptosis that may be associated with the selective members of caspase family.
Exp Mol Med 1999 Dec 31
PMID:Tanshinone IIA, an ingredient of Salvia miltiorrhiza BUNGE, induces apoptosis in human leukemia cell lines through the activation of caspase-3. 1063 Mar 70

Since HeLa cells possess very little functional p53 activity, they could be originally resistant to genotoxic stress-induced apoptosis. Therefore, it is likely that the drug-resistant cells derived from HeLa cells are more resistant to apoptosis. The aim of this study was to determine whether cisplatin-resistant cells derived from HeLa cells have an apoptosis-resistant phenotype. A cisplatin-resistant cell subline, HeLa/CDDP cells, showed a 19-fold resistance to cisplatin compared with the parent cells. The subline showed a collateral sensitivity to paclitaxel. An equitoxic dose (IC50) of cisplatin produced DNA fragmentation in HeLa cells but not in HeLa/CDDP cells. Transfection of wild-type p53 gene enhanced the cytotoxicity of cisplatin and cisplatin-induced apoptosis in HeLa cells but not in HeLa/CDDP cells, although it caused p53 overexpression in both cell lines. The expression of caspase 1 (interleukin-1beta-converting enzyme, ICE) mRNA and the overexpression of bax protein were observed only in HeLa cells. Paclitaxel-induced DNA fragmentation appeared less in HeLa/CDDP cells than in HeLa cells. p53 gene transfection did not affect the extent of DNA fragmentation in either cell line, suggesting that paclitaxel may induce p53-independent apoptosis. These findings suggest that HeLa/CDDP cells may have an acquired phenotype that is resistant to p53-dependent and -independent apoptosis.
Jpn J Cancer Res 1999 Dec
PMID:Cisplatin-resistant HeLa cells are resistant to apoptosis via p53-dependent and -independent pathways. 1066 56

Recently, we have demonstrated that ischemic preconditioning (IP) both limits infarct size and decreases internucleosomal DNA fragmentation in rat hearts in vivo, and that there was a direct correlation between myocardial infarct size and DNA fragmentation even after IP. In this study, we examined the ability of IP to attenuate processing and activation of caspase-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP), after prolonged ischemia and reperfusion using the same in vivo animal model. Rats that underwent IP and controls (Ctrl) were subjected to 30 min of left coronary artery occlusion followed by 180 min of reperfusion. IP was accomplished by five 5-min cycles of ischemia, each followed by 5 min of reperfusion. The amount of soluble nucleosomes was measured by enzyme-linked immunosorbent assay. Cleavage of caspases-1 and -3, and of one of their substrates PARP, was analyzed by Western blotting. Nucleosomal DNA fragmentation was significantly reduced in ischemic left ventricular (LV) tissue obtained from IP compared with Ctrl animals. The proforms of caspases-1 and -3, and the active form of PARP were not cleaved in the nonischemic LV region of both IP and Ctrl hearts. In contrast, the proform of caspase-3 and the active form of PARP were cleaved in the ischemic LV region of Ctrl hearts, while processing of caspase-1 was increased. Cleavages of caspases-1 and -3, and inactivation of PARP were prevented by IP. The results of this study indicate that IP attenuates both internucleosomal DNA fragmentation and caspases processing, and suggest that the prevention of caspases activation by IP may be important steps in protecting the heart against ischemia/reperfusion injury in vivo.
Cardiovasc Res 1999 Dec
PMID:Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo. 1069 Feb 85

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. During the last decade, a growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischaemia. The expression of IL-1 in the brain is dramatically increased during the early and chronic stage of infarction. The most direct evidence that IL-1 contributes significantly to ischaemic injury is that (1) central administration of IL-1beta exacerbates brain damage, and (2) injection or over-expression of interleukin-1 receptor antagonist, and blockade of interleukin-1beta converting enzyme activity reduce, dramatically, infarction and improve behavioural deficit. The mechanisms underlying IL-1 actions in stroke are not definitively elucidated, and it seems likely that its effects are mediated through stimulation and inhibition of wide range of pathophysiological processes.
J Neuroimmunol 1999 Dec
PMID:Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. 1069 31


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