Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bovine pulmonary endothelial (BPE) cell line was examined as a model to study the toxicity of ricin and abrin toxins currently under investigation. The BPE cell line was examined because ricin has been shown to bind to endothelial cells. Cell viability was assessed using several different biochemical parameters including growth (DNA by binding of gentian violet stain), mitochondrial function (succinate dehydrogenase activity) using MTT and lysosomal integrity (neutral red retention assay). In order to compare toxicities and investigate potential protective compounds, concentrations of toxins causing death of 50% and 70% of the (control) cell population (LC50 and LC70, respectively) were determined. It is concluded that while ricin and abrin share a common mechanism of action ricin is slightly less toxic than abrin. BPE cells are a good model for future mechanistic studies and particularly for initial phase screening of potentially therapeutic compounds. Carbohydrates were used in an attempt to examine which receptor types were involved in the binding and uptake of ricin and abrin by the cell line. It was found that only high concentrations of galactose prevented lethality while mannose apparently had no effect. Furthermore, the molar excess of carbohydrate to toxin required in order to achieve protection indicated that this would be an impractical approach to adopt in vivo.
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PMID:Examination of the toxicity of several protein toxins of plant origin using bovine pulmonary endothelial cells. 802 36

In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage cell lines, HD11 and MQ-NCSU, produced .NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of .NO produced. Using a modified MTT assay, .NO induced suppression in two mitochondrial complexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 +/- 5.5% suppression; complex II, 27.9 +/- 5.2%). In contrast, mitochondrial activities in samples receiving LPS plus inhibitor, NG-nitro-L-arginine methyl ester (NAME; 5 mM) or 2,4-diamino-6-hydroxypyrimidine (DAHP; 5 mM), were not significantly different from control values. When HD11 macrophages were cocultured with lymphoblastoid tumor targets, RECC-CU60 (T cell) or LSCC-RP9 (B cell), adding LPS (1 microgram/ml), tumor cell mitochondrial activity was significantly suppressed. In the generator macrophages, complex I was more suppressed than complex II, whereas in lymphoid targets no such difference was observed. These results indicate that .NO inhibits complex I and II mitochondrial activity but that differential targeting can occur among chicken leukocyte populations.
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PMID:Nitric oxide (.NO)-induced mitochondrial injury among chicken .NO-generating and target leukocytes. 802 70

The chemosensitivity of 43 human sarcoma tissues, including 18 osteosarcomas, 16 leiomyosarcomas and 9 liposarcomas, was compared with that of 28 adenocarcinomas of the stomach, using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues were exposed for 3 days to each antitumor drug, including adriamycin (ADM), 5-fluorouracil (5-FU), mitomycin C (MMC), cisplatin (CDDP), aclacinomycin A (ACR) and carboquone (CQ), them the cell viability was estimated based on the succinate dehydrogenase (SD) activity, determined using [3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H tetrazolium bromide] (MTT). SD activity was significantly lower in the osteosarcoma as compared to that in the adenocarcinoma, for ADM, MMC, CDDP, ACR and CQ (p < 0.01), and was higher for ADM (p < 0.05) in cases of leiomyosarcoma and for CDDP (p < 0.01) and ACR (p < 0.05) in cases of liposarcoma. The sensitivity rate was higher in osteosarcoma than in adenocarcinoma for ADM, MMC and CDDP. These findings suggest that patients with osteosarcoma will probably show a fairly good response to antitumor drugs, and that when liposarcoma or leiomyosarcoma tumors show resistance to antitumor drugs, then resection at the time of initial exploration and combined modalities, including radiation and hyperthermia, should be considered.
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PMID:Antitumor chemosensitivity differs between clinical sarcoma and adenocarcinoma tissues. 816 44

Early events in the cytotoxic response to tumour necrosis factor (TNF) of the murine fibrosarcoma cell lines L929 and WEHI164cl13 were assessed on a cell by cell basis using the fluorescent exclusion dye propidium iodide (PI) and analysis by flow cytometry. The rationale of this approach is based on the exclusion of PI by cells with intact membranes. PI-positive cells appeared within a few hours of TNF treatment and further accumulated with time at a TNF dose-dependent rate. Thus, TNF rapidly caused a breakdown of the barrier function of the membrane in these TNF-sensitive fibrosarcoma cell lines. On a time basis, membrane permeabilization was immediately followed by a sudden shrinkage of the cell and was accompanied by cell death, but preceded the inactivation of the mitochondrial succinate dehydrogenase by several hours. The latter enzymatic activity was measured by the MTT chromogenic assay. Cell death was determined on the basis of the capability of individual cells to produce a progeny in a clonogenicity assay. Both membrane permeabilization and cellular collapse were fast events that were completed within a very short time and may represent the direct cause for cell death. Opposed to this, loss of mitochondrial succinate dehydrogenase activity evolved more slowly, was initiated at a later time and apparently represents a post-lethal event, not directly linked to the TNF signal transduction pathway. Finally, the enhancing effect of the protein synthesis inhibitor cycloheximide on the various features of TNF-induced cytotoxicity was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell membrane permeabilization and cellular collapse, followed by loss of dehydrogenase activity: early events in tumour necrosis factor-induced cytotoxicity. 818 66

The possible existence of a threshold for compounds inducing chromosomal loss was investigated for four known aneugens (colchicine, COL; carbendazim, MBC; mebendazole, MEB; nocodazole, NOC) and two clastogens (methyl methanesulfonate, MMS; mitomycin C, MMC) using the micronucleus (MN) test in human lymphocytes. The presence of a whole chromosome in the MN was studied by fluorescent in situ hybridization (FISH) using a synthetic pancentromeric oligonucleotide probe. FISH was applied on two different MN preparations: cytokinesis-blocked MN (MNCB) assay, and MN sorted by flow cytometry. At subtoxic concentrations analyzed by MNCB and FISH, COL, MEB, MBC, and NOC induced a concentration-dependent increase in centromere-positive MN (MNCen+). MMC seemed to induce an increase in both types of MN (MNCen- and MNCen+), while MMS induced only MNCen-. On the sorted micronuclei (in a wide range of low to subtoxic concentrations), the concentration-effect profile for MNCen+, with the four aneugens tested, showed a statistically nonsignificant increase over a range of concentrations, followed by a second range of high concentrations with a statistically significant increase. To analyze the existence of a threshold, a piecewise linear regression was applied to the data. The first concentration that showed a statistically significant increase in MNCen+ was chosen as a breakpoint (0.037 microM for COL, 2.62 microM for MBC, 0.27 microM for MEB, and 0.066 microM for NOC). The statistical correlation between observed and predicted values showed a high correlation (r = 0.99), indicating a clear threshold for aneuploidy induction. However, for MMS the concentration-effect profile for MNCen+ showed a continuous concentration-dependent decrease with no threshold. With the two cytotoxicity assays used (Bio-Rad and MTT), no significant reduction was detected either in the protein content or in mitochondrial succinate dehydrogenase activity with all chemicals tested for MN induction. Therefore, our data suggest that the observed thresholds were not due to indirect toxic effects but to real aneugenic effects.
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PMID:Indications for a threshold of chemically-induced aneuploidy in vitro in human lymphocytes. 857 18

The acute toxicity of two degradable polymers, a 70:30 poly (L-D, L-lactide) (PLDLA) and a 90:10 poly(L-lactide-co-glycolide) (PLGA), was evaluated by the agar diffusion test and the filter test with L929 mouse fibroblasts. Extracts of the materials prepared in phosphate-buffered saline at 37 and 70 degrees C were assessed for mitochondrial succinate dehydrogenase activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA of BALB 3T3 cells. Both materials revealed no signs of cytotoxicity during the agar diffusions and filter tests. In the MTT and BrdU assays PLDLA and PLGA showed similar results. Cells treated with extracts prepared at 37 degrees C caused slight stimulation of mitochondrial activity. In contrast, cells incubated with the 70 degrees C media revealed a concentration-dependent decrease of mitochondrial activity. DNA synthesis was significantly decreased by the 37 degrees C extracts. As in the MTT assay, the effect of the extracts prepared at 70 degrees C was significantly greater. From these in vitro results it is suggested that PLDLA and PLGA have satisfactory biocompatibility. High concentrations of the degradation products, however, had a toxic influence on the cell culture systems used.
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PMID:In vitro biocompatibility of bioresorbable polymers: poly(L, DL-lactide) and poly(L-lactide-co-glycolide). 873 Sep 68

Cytotoxicity of benzo(a)pyrene (B(a)P), 7,12-dimethylbenz(a)anthracene (DMBA), aflatoxin B1 (AB1), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was estimated in vitro by using a hamster lung cell line. The studies were conducted to assess the usefulness of an organ-specific cell culture system for demonstrating differences in the cytotoxic potency of diverse chemical carcinogens. Cytotoxicity was determined by using the succinate dehydrogenase assay (MTT assay) after different incubation times and concentrations with the corresponding carcinogens. The effective concentration EC50 as well as the slope of the regression line were used as parameters for the biological effects. The results from these studies indicate a clear dose-dependent reaction after incubation of the cells with aflatoxin B1 (EC50: 2.3 microM) and MNNG (EC50: 4.0 microM). For the polycyclic hydrocarbons benzo(a)pyrene and DMBA, a dose-independent reaction was found. These results indicate that consideration of the EC50 values only might not be sufficient to characterize differences in the cytotoxic activity of different substances. Chemicals can lead to equal values in the EC50, but cells can differ significantly in their biological sensitivity, meaning that the extent of reduction in cell proliferation depends on the chemical used. By considering the two above-mentioned parameters, a ranking for the analyzed substances will be possible in the following way: AB1, MNNG, DMBA and B(a)P. Taken together, our experiments show that it is possible to reveal differences in the cytotoxic potency of chemicals by using in vitro methods.
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PMID:Sensitivity of a hamster lung cell line to direct and indirect acting carcinogens. 895 42

The activities of selected enzymes of the respiratory chain system in Onchocerca fasciata (Filarioidea: Onchocercidae) have been investigated histochemically. Thus, the localization and distributions of NADH dehydrogenase (EC 1.6.99.3), succinate dehydrogenase (SDH) (EC 1.3.99.1) and cytochrome oxidase (EC 1.9.3.1) were investigated in various tissues of the adult female worm by employing MTT, Nitro BT (dehydrogenases) and DAB (cytochrome oxidase). Different tissues varied considerably in their enzymatic activities. The hypodermis and reproductive tissues showed strong and identical localization of NADH and SDH dehydrogenase activities reflecting high metabolic rates. Little or no dehydrogenase activities were observed in the intestine and cuticle. In contrast to the two dehyrogenases, no activity was observed for cytochrome oxidase in any of the tissues in adult or embryonic stages of the worm. The significance of these results with respect to the energy metabolism of the worm is discussed. It is suggested that O. fasciata lacks a classical, mammalian-type respiratory pathway and that oxidative phosphorylation is of no importance as an energy generating pathway in this essentially anaerobic parasite.
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PMID:Onchocerca fasciata: histochemical demonstration of succinate and NADH dehydrogenase. 896 Jan 99

Indicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor-plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride ([Au(DPPE)2]Cl), CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rh123), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-Sla was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.
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PMID:Serine protease inhibition and mitochondrial dysfunction associated with cisplatin resistance in human tumor cell lines: targets for therapy. 926 20

When epithelial cells reach confluency in vitro, a number of energy-requiring activities such as growth and motility are contact-inhibited. We investigated the possible role of the E-cadherin/catenin complex, which acts as an invasion suppressor, in contact inhibition. Three strategies for modulation of the complex were used. Firstly, the cell-cell adhesion and signal transduction functions of E-cadherin were neutralized immunologically in human MCF-7/6 mammary carcinoma cells possessing a complete complex. Secondly, the effect of E-cadherin transfection in E-cadherin negative cell lines was investigated. Thirdly, alpha-catenin deficient variants of the human HCT-8/S11 colon carcinoma cell line were compared with their parent cells. In confluent cultures functional downregulation of the E-cadherin/catenin complex did not alter cell growth nor saturation density. This was shown by cell number counts, protein staining assays, cell cycle analysis, proliferation markers (Ki67 and Proliferating Cell Nuclear Antigen) and apoptosis assays. However, confluent cells with a functionally deficient complex showed positional instability and enhanced succinate dehydrogenase-mediated mitochondrial 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl) tetrazolium bromide (MTT) conversion, as compared to cells with an active complex. Our data indicate that contact inhibition of motility and of mitochondrial enzyme activity, but not of growth is regulated by the E-cadherin/catenin complex in epithelial cells.
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PMID:Functional downregulation of the E-cadherin/catenin complex leads to loss of contact inhibition of motility and of mitochondrial activity, but not of growth in confluent epithelial cell cultures. 943 30


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