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

Modification of the silica surface has been shown to reduce its cytotoxicity in vitro and its fibrogenic activity in vivo. We have shown silica to be a potent stimulator of arachidonic acid (AA) metabolism in bovine alveolar macrophages (BAM). To determine the effect of surface-modified silica on AA metabolism in BAM, we exposed BAM in vitro to silica treated with aluminum lactate or polyvinylpyridine-N-oxide (PVPNO). BAM were prelabeled with [3H]AA and incubated with 3 and 5 mg of silica. Unmodified silica at these doses elicited maximal AA metabolite release from BAM. AA metabolites were analyzed by high performance liquid chromatography. Lactate dehydrogenase release was quantitated to determine the cytotoxicity of treated and untreated silica on BAM. Treating silica with aluminum lactate or PVPNO significantly (P less than or equal to 0.05) reduced 5-lipoxygenase metabolite release and significantly (P less than or equal to 0.05) increased cyclooxygenase metabolite release. These changes in AA metabolite release were accompanied by a significant (P less than or equal to 0.05) reduction in the cytotoxicities of the treated silicas compared with untreated silica. Our results suggest that the reduced inflammatory and fibrogenic activity of surface-modified silica may in part be due to reduced AA metabolite release from exposed macrophages.
Am J Respir Cell Mol Biol 1992 May
PMID:Diminished arachidonic acid metabolite release by bovine alveolar macrophages exposed to surface-modified silica. 131 33

In the present study the acute effect of intravenous aluminum chloride (1 mg/kg) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities of rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB) as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min after femoral vein injection. Two hours following aluminum injection, ChAT activity in the basal forebrain and hippocampus was significantly reduced by 30% and 22%, respectively, whereas no change was observed in the caudate nuclei. On the other hand, AChE activity was significantly increased by 45% in the caudate nuclei, whereas little change was observed in other brain areas. This report demonstrates that rapid transport of Al across the BBB, and the acute nature of Al neurotoxicity in rats.
Mol Chem Neuropathol 1992 Aug
PMID:Aluminum-induced acute cholinergic neurotoxicity in rat. 138 51

The alveolar macrophage (AM) is likely to play a central role in the initiation and development of the fibrosis associated with asbestos exposure due to its ability to produce factors that modulate cellular functions of the immune system of the lung. In this study, we examine the effects of IgG, albumin, and dipalmitoylphosphatidylcholine (DPPC), the major protein and lipid constituents of alveolar lining fluid, on the interaction between the human AM and chrysotile and crocidolite asbestos, silica, and aluminum beads. We show that both chrysotile and crocidolite asbestos, but not silica and aluminum beads, stimulate the human AM to produce superoxide anion. Preincubating chrysotile and crocidolite asbestos with IgG resulted in an enhancement of their ability to stimulate superoxide anion production. IgG subclasses were studied to determine the subclass specificity of this enhancing effect; on a molar basis, IgG1 was the most potent. After preincubation with IgG, both silica and aluminum also stimulated superoxide anion production to levels similar to the IgG-preincubated asbestos. When albumin and DPPC were included in the preincubation mixture, the IgG-mediated enhancement of superoxide anion production by asbestos was unaffected, while that of silica and aluminum was abolished. In summary, these results indicate that IgG can significantly enhance the bioactivity of particulates for human AM in vitro, and that chrysotile and crocidolite asbestos are unique in their ability to retain this enhancement in the presence of albumin and DPPC. These results are consistent with the suggestion that superoxide anion production by the AM may play an important role in the development of asbestosis.
Am J Respir Cell Mol Biol 1991 Jun
PMID:In vitro bioactivity of asbestos for the human alveolar macrophage and its modification by IgG. 164 78

Intracellular Ca2+ mobilization events were assessed in mouse L cells, which contain native prostaglandin E1 receptors and transfected human beta 2 adrenergic receptors. Both Fura2 (single cell measurements) and Quin 2, (cuvette assays) were used to determine [Ca2+]i levels. Our results demonstrate that in the transfected cells there is a dose-dependent increase in [Ca2+]i in response to isoproterenol (0.1 nM-100 nM), which is inhibited by the beta-adrenergic antagonist, propranolol, and is a result of intracellular Ca2+ release. [Ca2+]i in these cells was also increased by prostaglandin E1, 8 bromo cyclic AMP, and aluminum fluoride. Both 8 bromo cAMP and isoproterenol induced a rapid increase in the levels of IP1, IP2, and IP3. The data presented demonstrate that the elevation of intracellular cyclic AMP induces an increase in IP3 production which leads to an elevation in [Ca2+]i. We propose that this cyclic AMP dependent activation of the IP3 generating system occurs at a post-receptor site.
Mol Cell Biochem 1991 Feb 27
PMID:Activation of the inositol trisphosphate second messenger system by cAMP in a mouse fibroblast cell line. 184 29

Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE 85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.
Mol Cell Biochem 1991 Jul 10
PMID:Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride. 192 12

The presence of the trivalent metallic cations, aluminum and boron, in the culture medium of differentiated human LAN-5 neuroblastoma cells results in increased amounts of specific isomers of microtubule-associated tau proteins. The cells were differentiated to a neuronal phenotype by the addition of retinoic acid. Six-day exposures of the differentiated cells to a 1-mM dose of aluminum or boron yielded increases in tau protein immunoreactivity to the monoclonal antibodies Tau-1 and Alz-50. Significant increases in immunoreactivity were seen at treatment levels of aluminum down to 100 microM. The increases in tau proteins were independent from increases in levels of total cell protein. Control cultures treated with the divalent cations zinc and iron showed no increases in levels of tau proteins.
Mol Chem Neuropathol 1991 Jun
PMID:Effects of aluminum on tau proteins in human neuroblastoma cells. 195 63

Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of diacylglycerol and inositol 1,4,5-triphosphate. We showed that following stimulation by PDGF, rat-2 cells overexpressing PLC-gamma 1 display an increase in the levels of both tyrosine-phosphorylated PLC-gamma 1 and inositol phosphates compared with the parental rat-2 cells. This increased responsiveness to PDGF is a direct effect of PLC-gamma 1 overexpression, as a cell line expressing similar levels of an enzymatically inactive point mutant of PLC-gamma 1, PLC-gamma 1 335Q, did not show elevated inositol phosphate production in response to PDGF. Hematopoietic cells express PLC-gamma 2, a PLC isoform that is closely related to PLC-gamma 1. When rat-2 cells overexpressing PLC-gamma 2 were treated with PDGF, an increase in both the tyrosine phosphorylation and the in vivo activity of PLC-gamma 2 was observed. Aluminum fluoride (AIF4-), a universal activator of PLC linked to G-proteins, did not produce an increase in the levels of inositol phosphates in either of the overexpressing cell lines compared with parental rat-2 cells, demonstrating that PLC-gamma isoforms respond specifically to a receptor with tyrosine kinase activity.
Mol Cell Biol 1991 Apr
PMID:Platelet-derived growth factor increases the in vivo activity of phospholipase C-gamma 1 and phospholipase C-gamma 2. 200 95

1. Aluminum administration to susceptible animal species results in neurofilament accumulation in neuronal perikarya and proximal axons. Pathogenetic studies in vivo have shown that aluminum rapidly associates with neuronal chromatin. Whether the effect of aluminum on DNA components plays a role in the production of the neurofibrillary lesion remains unclear. 2. In this study we used Northern analysis and in situ hybridization to evaluate mRNA levels of specific neuronal and glial components in the rabbit spinal cord at various times following aluminum administration. 3. Our results show that (a) all neuronal mRNAs evaluated (neurofilament triplet components, neuronal-specific enolase, and amyloid precursor protein) are markedly decreased, with no decrease in glial fibrillary acidic protein; (b) the effect on neuronal gene expression occurs early and concurrently with the development of the neurofibrillary lesion and reverses rapidly after a single dose of aluminum; and (c) there is a direct correlation between the severity of the neurofibrillary lesion and the decrease in neuronal mRNA levels. 4. We interpret our results to mean that the accumulation of neurofilaments in this model is not due to a selective effect on neurofilament gene expression but may be due to an inhibition of genes coding for components involved in processing of neurofilament proteins.
Cell Mol Neurobiol 1989 Mar
PMID:Neuronal gene expression in aluminum myelopathy. 249 32

A new sampling method of cross-sectioning the canine heart in situ was developed. A mechanical device, driven by spring power, enabled cross-sectioning of a short-axis plane of the beating canine heart (4 mm thick) with high speed rotating blades, at a pre-determined phase of the cardiac cycle, and instantaneous freeze-clamping (2.4 mm thick) with pre-cooled aluminum blocks, all within 120 ms. By this method, the anatomical structures of the sample were well preserved. Transmural metabolism and flow distribution were instantaneously fixed and high resolution of the two-dimensional redox state was obtained by application of NADH fluorescence photography. Micro-samplings from the desired portion of the cross-sectional slice were possible at -190 degrees C. NADH fluorescence of the samples did not increase from the surface to 1.2 mm in depth, confirming that there was no ischemic artifact. With the present technique, a heart sample in which transmural metabolism, and the redox state, are fixed and visualized is attainable, thus providing a new tool for the study of myocardial ischemia.
J Mol Cell Cardiol 1989 Feb
PMID:A rapid cross-sectioning and freeze-clamping device for the beating canine heart. 266 89

High-precision solution densimetry was used to determine volume parameters for the interaction of inhalation anesthetics with water, nonpolar solvent, and phospholipid vesicles. The precision of the densimeter is mainly limited by the constancy of the temperature during measurement. Therefore, temperature stability was maintained within +/- 0.0005 degrees and monitored by a microprocessor-controlled Thermistor thermometer with 0.0001 degrees resolution. All values were obtained at 25 degrees. Because volatile anesthetics in liquid form usually contain water, they were purified by passage through activated aluminum oxide columns. The molal volumes of dried preparations at the pure liquid states were: halothane, 106.3(3); isoflurane, 123.6(6); and enflurane, 121.9(9) cm3 X mole-1 at 298.150 degrees K. The mean molal excess volumes of anesthetic-water mixtures were negative at dilute anesthetic concentrations in water and positive at dilute water concentrations in liquid anesthetics. These values were dependent on the mole fractions of each component and showed a minimum in the water-rich region and a maximum in the anesthetic-rich region. In water, the partial molal volumes were halothane 93.7, isoflurane 103.4, and enflurane 98.6 cm3 X mole-1 at infinite dilution, and increased as the anesthetic concentration was increased. The partial molal volumes of water in liquid anesthetics were in halothane 21.7, isoflurane 21.0, and enflurane 20.5 cm3 X mole-1 at infinite dilution, and decreased as the anesthetic concentration was decreased. The mean excess volumes of the anesthetic-decane mixture were positive in the entire mixing range. The partial molal volumes of anesthetics in n-decane at infinite dilution were halothane 114.9, isoflurane 135.3, and enflurane 135.2 cm3 X mole-1. The mean specific excess volumes of the mixture of anesthetics and dimyristoylphosphatidylcholine vesicle suspension showed positive values. The partial molal volume was not evaluated because of the theoretical difficulty in estimating it in a dispersed two-phase system. Because the mean excess volume of anesthetics dissolved in water is always negative and that incorporated into phospholipid suspension is positive, anesthetics expand the total volume of the model membrane system when translocated from water to the membrane. Anesthesia occurs when the mean excess volume of the total system exceeds a limiting value, and the bulk membrane size is irrelevant. Although the present result in no way disclaims alternative hypotheses, it demonstrates that the pressure reversal of anesthesia can be explained without assuming any specific receptors for these anesthetics.
Mol Pharmacol 1984 Jan
PMID:Membrane expansion and inhalation anesthetics. Mean excess volume hypothesis. 654 81


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