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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,1,1-Trichloroethane is a widely used solvent that is annually linked to several cases of sudden death following accidental exposure or abuse. Sudden death is believed to be due to ventricular fibrillation or myocardial depression. The purpose of this study was to investigate the mechanism of myocardial depression by assessing the influence of 1,1,1-trichloroethane on intracellular Ca transients in single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-Ca binding. Cells were exposed to 1,1,1-trichloroethane in Hanks' balanced salt solution aliquoted as a 0.2% DMSO solution by a single pass suffusion in an environmentally controlled chamber. 1,1,1-Trichloroethane (0.25 mM-8 mM) reduced the height of electrically (1 Hz, 60 V, 10 ms) induced Ca transients concentration dependently and reversibly to a maximum of about 50% with no effect on diastolic Ca concentration. Video motion analysis revealed an inhibition of contractility in the same concentration range. 1,1,1-Trichloroethane inhibited cytosolic Ca increase in response to KCl-induced (90 mM) depolarizations and further decreased the limited Ca transients in ryanodine (1 microM) pretreated myocytes. Increased external Ca (5 mM) antagonized the effect of 0.5 mM 1,1,1-trichloroethane on the Ca transients. 1,1,1-Trichloroethane reduced the caffeine (10 mM) releasable Ca pool in myocytes. These results show that 1,1,1-trichloroethane inhibits Ca mobilization during excitation-contraction coupling in ventricular myocytes. An inhibitory action on the influx of extracellular Ca as well as on sarcoplasmic reticulum Ca release and sequestration is likely to be responsible for this action.
J Mol Cell Cardiol 1992 Jun
PMID:Calcium transients in isolated cardiac myocytes are altered by 1,1,1-trichloroethane. 151 78

Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione. Extracellular H2O2 generation was determined spectrofluorometrically using 3-methoxy-4-hydroxy phenylacetic acid, and intracellular H2O2 production (in or near peroxisomes) was measured indirectly using aminotriazole, which inactivates catalase in the presence of H2O2. Extracellular H2O2 release was 0.079 +/- 0.005 nmol/min/mg protein in Hanks' balanced salt solution, was constant during a 120-min incubation period, and was not affected by the cell passage number. The half-life for catalase inactivation with aminotriazole was 23 min. Inhibition of catalase, glutathione reductase, or gamma-glutamylcysteine synthetase did not change the rate of extracellular release of H2O2. Furthermore, inhibition of the mitochondrial respiratory chain (rotenone, antimycin A) or microsomal cytochrome P-450 (8-methoxypsoralen) did not change extracellular H2O2 release or intracellular H2O2 production (at peroxisomes) by endothelial cells or cells in which glutathione reductase was inactivated. When the cells were exposed to exogenous H2O2 (30 microM), extracellular H2O2 was scavenged primarily by the glutathione redox pathway. Exogenously added H2O2 (100 microM) changed intracellular H2O2 production (in or near peroxisomes) only when the glutathione redox cycle was inactivated. Menadione (20 microM), which undergoes intracellular redox cycling, increased extracellular H2O2 release almost 4-fold to 0.3 nmol/min/mg protein. Furthermore, menadione increased peroxisomal H2O2 levels and decreased the half-life for catalase inactivation in the presence of aminotriazole to 13 min. Catalase inhibition increased extracellular H2O2 release during menadione treatment, indicating that H2O2 can diffuse across the plasma membrane during oxidant stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Feb
PMID:Regulation of hydrogen peroxide generation in cultured endothelial cells. 154 Mar 80

Murine, antihuman melanoma cell monoclonal antibody (mAb) 16.C8 was generated by fusing the murine myeloma cell line P3X63/Ag8.653 with splenocytes from a nude mouse bearing a human melanoma xenograft, after reconstitution with splenocytes from syngeneic immunocompetent BALB/c mice. The antibody reacted strongly with fresh human melanoma cells and exhibited preferential reactivity with established human melanoma and neuroectodermal tumor cell lines. Electrophoresis and Western blotting experiments indicated that 16.C8 is directed against a sialoglycoprotein antigen with a molecular weight of 110-120 kDa. mAb 16.C8 mediated lysis of melanoma cells in vitro in antibody-dependent cellular cytotoxicity assays using human mononuclear effector cells isolated from normal volunteers or malignant melanoma patients. In addition, the administration of mAb 16.C8 to nude mice bearing established human melanoma lung and liver metastases resulted in significant inhibition of tumor growth as shown by gross and histologic examination. In contrast, animals treated with Hanks' balanced salt solution or nonspecific immunoglobulin exhibited a large tumor burden. These results suggest that mAb 16.C8 may be of value in treatment of metastatic melanoma in humans.
Mol Biother 1991 Sep
PMID:Cell binding and tumor inhibiting functions of a new antihuman melanoma murine monoclonal antibody. 176 67

Leishmania major promastigotes were grown to late log phase, washed and resuspended in Hanks' balanced salt solution, and incubated with glucose at various pO2s in the presence of 5% CO2. Samples were taken at times from 0-40 min and assayed for fructose 2,6-bisphosphate (Fru(2,6)P2), glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), phospho(enol)pyruvate (PEP), and ATP. At 95% O2 ATP remained constant throughout the incubation. It did not decrease significantly at 10% O2, but decreased by about 20% and 30% at 6% and 0% O2, respectively. At 95% O2, Fru(2,6)P2 increased about 15-fold within 5 min after the addition of glucose and remained at this high level. At 10%, 6%, and 0% O2 Fru(2,6)P2 rose about 5-fold within 5 min and then declined slightly during the remainder of the incubation. G6P increased from about 0.5 to 12 nmol (mg protein)-1 at 5 min in cells incubated under 95% O2 and then declined to about 5 nmol (mg protein)-1. It increased to about 8 nmol (mg protein)-1 at 5 min and then declined slightly in cells incubated under 10% O2. F6P levels were approximately one-eighth of G6P levels under all conditions, suggesting that phosphohexoseisomerase was not subject to regulation. PEP levels were initially high, but at 95% O2 there was a 50% drop in PEP at 5 min, while at 10%, 6%, and 0% O2 there was less of a decline. The observation that the rise in Fru(2,6)P2 levels at 10%, 6%, or 0% O2 is the same at 5 min and less than the rise at 95% O2 supports the presence of a low affinity oxygen sensor. The different time course of changes in G6P, F6P, and PEP levels suggests that in addition to an activation of pyruvate kinase by Fru(2,6)P2, other regulatory events are also operative at low pO2.
Mol Biochem Parasitol 1991 Aug
PMID:Changes in intracellular levels of fructose 2,6-bisphosphate and several glycolytic intermediates in Leishmania major promastigotes as a function of pO2. 194 14

We have evaluated the participation of the lysosomal degradation pathway in the increased protein degradation induced by nutrient deprivation in transformed cells. To this end we used a clone, 12-1a, derived from a murine teratocarcinoma cell line (F9 12-1) induced to differentiate by culture in retinoic acid. Culture of 12-1a cells, prelabeled with L-[U-14C]valine, in nutrient-deprived medium (Hanks' balanced salt solution plus Ca++) stimulated the protein degradation rate from 0.9% hr to 1.4% hr. Morphometric analysis demonstrated that during nutrient deprivation, the volume density of lysosomes increased 3-fold; the numerical density of lysosomes increased 2-fold; the mean area of lysosomal profiles increased 1.7-fold (1.40 microns2 vs 0.81 microns2). The volume density and numerical density of the dense bodies tended to decrease by approximately 60% without any change in the mean volume of the dense bodies. These data indicate that nutrient deprivation increases protein degradation in transformed cells by increasing the sequestration of cytoplasm into the lysosomes. The decrease in the number of dense bodies indicates that these structures (also termed residual bodies) are functional in transformed cells and merge with the lysosomes to provide more degradative enzymes to enhance proteolysis. This study provides direct evidence that serum factors and nutrients play a crucial role in modulation of lysosomal protein degradation in transformed cells.
Exp Mol Pathol 1989 Feb
PMID:Stimulation of autophagic protein degradation by nutrient deprivation in a differentiated murine teratocarcinoma (F9 12-1a) cell line. 264 43

The ability of Schistosoma mansoni schistosomula to evade in vitro cytotoxic activity of antibodies plus complement is shown to be increased by incubation with Concanavalin A (Con A) or with non-immune inactivated human serum. This effect was not observed if S-adenosyl-homocysteine (SAH) a methyltransferase inhibitor was added to the incubation medium. Methyl group incorporation occurs in schistosomulum phospholipids if parasites are incubated in Earle's balanced salt solution. This incorporation is increased by Con A addition and this increase is inhibited by SAH. Supernatants of schistosomula incubated in culture media containing Con A were able to promote phospholipid methylation, showing that methyltransferases were liberated into the culture media. The possible roles played by these phenomena in host-parasite interactions are discussed.
Mol Biochem Parasitol 1986 Nov
PMID:Schistosoma mansoni: phospholipid methylation and the escape of schistosomula from in vitro cytotoxic reaction. 378 93

Several approaches to surface membrane stripping have been applied to the adult schistosome. Membrane removal was evaluated by the use of different extrinsic and intrinsic markers of which alkaline phosphatase proved to be the most reliable. After initial studies employing incubation of worms in buffer alone, Triton X-100 or freeze/thaw, the last method was chosen for development. The final method applies a single freeze/thaw step to adult worms in balanced salt solution followed by short bursts of agitation on a vortex mixer to release the tegument. Differential and density gradient steps subsequently yield a final membrane pellet enriched over 130 times in surface alkaline phosphatase. The method has been characterized during its development using electron microscopy and enzyme markers for contaminant worm fractions.
Mol Biochem Parasitol 1983 Oct
PMID:Tegument surface membranes of adult Schistosoma mansoni: development of a method for their isolation. 666 62

Solid tumors elaborate soluble substances that (directly or indirectly) induce angiogenesis by a step-wise process which ultimately results in a microvascular network that nourishes the growing tumor. To study angiogenesis induced by brain tumors we have used a rat glioma model. Modifying the disc angiogenesis system (DAS) we evaluated quantitatively the angiogenic response to cultured, live RT-2 rat glioma cells placed in the center of the discs. DAS were implanted in the subcutaneous tissue of rats and evaluated for vessel proliferation 2 weeks later. Recognition of vessels was greatly facilitated by the staining of their basement membrane using a polyclonal anti-collagen IV antibody. Experimental discs containing 10(3) or 10(5) glioma cells as well as positive control discs containing the agonist prostaglandin E1 consistently demonstrated greater vessel growth than negative controls (discs containing a balanced salt solution). The disc angiogenesis system is a useful tool for the measurement of angiogenic response to living tumor cell suspensions.
Exp Mol Pathol 1993 Apr
PMID:Application of the disc angiogenesis system to tumor-induced neovascularization. 768 37

The basis for surfactant accumulation after silica exposure is not known. As a result of an association between elevations in extracellular surfactant and oxidant exposures, we tested the hypothesis that (1) surfactant-enriched material can function as an in vitro target for oxidants catalyzed by Fe3+ complexed to the surface of silica, and (2) in vivo alveolar accumulation of surfactant after exposure of the lower respiratory tract to silica is associated with the concentration of Fe3+ complexed to the dust surface. Surfactant-enriched material was incubated in both chemical and cellular systems with either Gey's balanced salt solution, acid-washed silica, deferoxamine-treated silica, wetted silica, or iron-loaded silica. The absorbance of oxidized products was associated with concentrations of complexed iron on the surface of the silica dust. Rats (n = 10/group) were intratracheally instilled with either normal saline, 6.0 mg acid-washed silica, 6.0 mg deferoxamine-treated silica, 6.0 mg wetted silica, or 6.0 mg iron-loaded silica. Ninety-six hours after tracheal instillation, silica significantly increased extracellular surfactant as reflected by lipid phosphorous in the total lavage fluid. Lipid accumulation was associated with concentrations of surface complexed iron on the surface of the silica.
Am J Respir Cell Mol Biol 1993 Apr
PMID:Lavage phospholipid concentration after silica instillation in the rat is associated with complexed [Fe3+] on the dust surface. 838 35

Nitric oxide synthase (NOS) is responsible for the biological production of nitric oxide (NO) in several organs. NOS activity has also been localized in the reproductive tract, although direct evidence for its presence in the human or bovine oviduct is still lacking. In the present study, four different techniques were used to identify the presence of NOS activity in human (n = 11) and bovine (n = 9) oviduct: (i) conversion of [3H]-L-arginine to [3H]-L-citrulline; (ii) production of nitrite/nitrate (NO2/NO3; stable NO metabolites); (iii) identification of NADPH-diaphorase activity; and (iv) immunostaining with antiserum to endothelial NOS. Cytosolic extracts from human ampullary segments of the Fallopian tube, obtained from post-partum patients (n = 4), converted [3H]-L-arginine to [3H]-L-citrulline (21.0 +/- 8.8 fmol/mg protein/min). This conversion rate was significantly (P < 0.05) reduced in the presence of either EDTA or N-monomethyl-L-arginine monoacetate (L-NMMA), an inhibitor of NOS activity. When bovine (n = 3) ampullary segments were incubated for 36 h in Hanks' balanced salt solution, the concentration of NO2/NO3 in the medium was increased (P < 0.05) if segments were pretreated with lipopolysaccharide (LPS; an inducer of inducible NOS), but not after treatment with LPS + L-NMMA. Additionally, epithelial cells cultured from ampullary segments showed positive staining both for NADPH-diaphorase activity and with antiserum to endothelial NOS. The results of the present study provide direct evidence for the presence of both the Ca(2+)-dependent constitutive form of NOS, as well as the inducible form of NOS activity in human and bovine oviduct. Since the oviduct plays a key role in the reproductive process, it is possible that the two forms of NOS may be involved in the physiological regulation of oviduct function.
Mol Hum Reprod 1996 Aug
PMID:Identification of nitric oxide synthase in human and bovine oviduct. 923 73


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