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

Hexavalent chromium compounds are carcinogenic to humans, are potent inducers of tumors in experimental animals, and can neoplastically transform cells in culture. In this study, the effects of sodium chromate on the expression of the 78-kDa glucose-regulated protein (GRP78) gene and on general transcription were investigated with respect to the DNA damage induced by this agent. DNA single-strand breaks, DNA-protein cross-links, and chromium-DNA adducts were present in CHO cells immediately after 2 h of treatment with sodium chromate. Subsequently, these types of damage were repaired at different rates. Single-strand breaks were essentially repaired after 8 h. By 24 h posttreatment, no cross-links remained in cells exposed to 30 or 150 microM chromate, although cells treated with the 300-microM concentration still contained cross-links at that time. DNA-chromium adducts remained unrepaired for at least 32 h. The moderate constitutive level of GRP78 mRNA was not affected by chromate. Chromate did, however, suppress induction of this gene by tunicamycin in a concentration-and time-dependent manner. Thirty micromolar sodium chromate (96% survival), which caused the least DNA damage, had no effect on GRP78 induction, general RNA synthesis, or mRNA synthesis. Induction of GRP78 was suppressed immediately and 12 h after treatment with 150 microM chromate (54% survival), although there was a partial recovery of induction at 24 h after treatment, which correlated with the repair of DNA-protein cross-links. In contrast, both total cytoplasmic RNA and mRNA synthesis were suppressed by approximately 60-75% for at least 32 h by 150 microM chromate. At the 300-microM concentration (8% survival), where DNA-protein cross-links persisted beyond 24 h, GRP78 induction was totally suppressed for at least 24 h, while total RNA and mRNA synthesis were suppressed by 80-90% for at least 32 h. Overall, the effects of chromate on GRP78 induction correlated most closely with the presence of DNA-protein cross-links, but suppression of total RNA and mRNA synthesis correlated with the presence of DNA-chromium adducts. These results indicate that chromate exerts differential effects on the induction of the GRP78 gene and on general transcription.
Mol Carcinog 1992
PMID:Transcriptional inhibition by carcinogenic chromate: relationship to DNA damage. 128 64

Pentoxifylline, a methylxanthine with phosphodiesterase inhibitor activity, attenuates endotoxin-induced pulmonary vascular protein leak and decreases lung neutrophil accumulation in vivo. In vitro, pentoxifylline decreases neutrophil activation as measured by superoxide release and phagocytosis of latex beads. To test the hypothesis that the beneficial effect of pentoxifylline may be via a direct effect on the endothelial cells as well as via prevention of neutrophil activation, we incubated bovine pulmonary artery endothelial cell monolayers with endotoxin and pentoxifylline in the presence or absence of human neutrophils. Albumin clearance across the monolayers was used as an index of endothelial permeability. Endotoxin (1.0 micrograms/ml) increased albumin clearance in a dose- and time-dependent fashion (207.5 +/- 25%, P less than 0.05). Co-incubation with neutrophils enhanced this effect. Pentoxifylline significantly attenuated the endotoxin-induced increase in albumin clearance both with and without neutrophils, and lessened endotoxin-induced cell lysis (chromium release) and morphologic changes. Because increased endothelial cyclic adenosine monophosphate (cAMP) levels may decrease protein permeability and pentoxifylline increases cAMP in neutrophils, we measured cAMP levels in endothelial cells. Incubation with pentoxifylline failed to raise cAMP levels in endothelial cells, in contrast to incubation with aminophylline. In conclusion, pentoxifylline attenuates endotoxin-induced increase in albumin clearance across endothelial monolayers both in the presence and absence of neutrophils. These results suggest that part of the protective effect of pentoxifylline may be mediated via effects on endothelium. Furthermore, this pentoxifylline-mediated endothelial barrier effect appears to be independent of an effect on cAMP.
Am J Respir Cell Mol Biol 1991 Mar
PMID:Pentoxifylline lessens the endotoxin-induced increase in albumin clearance across pulmonary artery endothelial monolayers with and without neutrophils. 184 85

We investigated DNA damage caused by carcinogenic metals in a murine sarcoma virus (MuSV)-based mutagenicity assay in which mutations targeted to v-mos expression can be selected. Nickel chloride treatment of NRK cells (termed 6m2 cells) infected with MuSVts110, a retrovirus conditionally defective in viral RNA splicing and cell transformation, caused the outgrowth of transformed "revertants" with changes in the MuSVts110 RNA splicing phenotype. Cadmium and chromium treatment of 6m2 cells resulted in the selection of a second class of revertants with what appeared to be frameshift mutations allowing the translation of a readthrough gag-mos protein. In both classes of metal-induced revertants, viral gene expression was distinct from that observed in revertants arising in untreated 6m2 cultures, arguing that metal treatment did not simply enhance the rate of spontaneous reversion. In one representative nickel revertant line the operative nickel-induced mutation affecting MuSVts110 RNA splicing was a duplication of 70 bases surrounding the 3' splice site. The effect of this mutation was to direct splicing to the most downstream of the duplicated 3' sites and concomitantly relax its characteristic thermosensitivity. These data establish the mutagenic potential of nickel and provide the first example of a defined nickel-induced mutation in a mammalian gene.
Mol Carcinog 1991
PMID:Nickel mutagenesis: alteration of the MuSVts110 thermosensitive splicing phenotype by a nickel-induced duplication of the 3' splice site. 184 87

The effect of DNA damage induced by the carcinogen chromium(VI) on the function of DNA as a template for transcription of constitutive and inducible genes was examined in chick embryo liver in vivo. Changes in gene expression, determined using solution hybridization and northern blot analyses to measure steady-state mRNA levels and a nuclear run-off assay to measure gene transcription rates, were compared to chromium-DNA binding and to chromium(VI)-induced DNA damage as previously measured by DNA alkaline elution. Chromium(VI) treatment had little or no effect on either the steady-state mRNA levels or the transcription rates of the constitutively expressed genes for albumin, conalbumin (avian transferrin), or beta-actin. In contrast, chromium(VI) treatment had significant but opposite effects on the basal and drug-inducible expression of 5-aminolevulinate synthase and cytochrome PB1 P450. The changes in steady-state expression of these two inducible genes were similar to the changes in transcription rate, indicating that the effects of chromium were principally transcriptional. Chromium(VI) treatment increased the basal expression of both inducible genes four- to fivefold at maximum, and the time course of this effect was similar to the time course for chromium(VI)-induced DNA damage and repair. In contrast, chromium(VI) pretreatment suppressed by 60-70% at maximum the subsequent induction of these genes by glutethimide, a phenobarbital analog, and the time course of this effect also corresponded to that of chromium(VI)-induced DNA damage and repair. The time courses of the changes in expression of these genes were bimodal, with the second peak corresponding closely to that of chromium(VI)-induced DNA cross-links. However, the first peak occurred during a period when no DNA cross-links or strand breaks were detectable by alkaline elution, although significant levels of chromium were bound to DNA. This suggests that chromium(VI), like cisplatin, may initially produce a DNA monoadduct that subsequently leads to DNA cross-link formation and that both types of chromium(VI)-induced lesions have a significant effect on the expression of targeted genes.
Mol Carcinog 1989
PMID:Differential effects of chromium(VI) on constitutive and inducible gene expression in chick embryo liver in vivo and correlation with chromium(VI)-induced DNA damage. 260 65

Potassium chromate induced the formation of DNA-protein complexes in cultured Chinese hamster ovary cells. The DNA-protein complexes were isolated by ultracentrifugal sedimentation in the presence of 2% sodium dodecyl sulfate (SDS) and 5 M urea. Two-dimensional SDS-polyacrylamide gel electrophoresis analysis of the chromate-induced DNA-protein complexes revealed that two acidic proteins of 53 and 45 kDa and a basic protein of 54 kDa were selectively complexed to the DNA. Numerous other proteins also became associated with the DNA to a lesser degree as the chromate concentration was increased. Nuclease digestion was not a prerequisite for the resolution of the protein component of the DNA-protein complexes using two-dimensional gel electrophoresis. Ultracentrifugal analysis of the DNA-protein complexes in the presence of proteinase K, nucleases, or a chelating agent demonstrated that protein aggregation was not responsible for the increased protein recovery in chromate-treated samples and that the complexes were disrupted by EDTA. These data suggest that the selectively complexed proteins were associated with the DNA through strong interactions that may be mediated by the trivalent form of chromium.
Mol Carcinog 1988
PMID:Characterization of DNA-protein complexes induced in intact cells by the carcinogen chromate. 315 Dec 60

Chromium, in its various forms, is recognized both as a human carcinogen and as a nutrient essential in glucose homeostasis. Although the genotoxicity of this element is associated with its carcinogenic properties, the manner in which chromium mediates its epigenetic effects on cells, including its ability to potentiate insulin action, is not known. In the current studies, Western blotting with antiphosphotyrosine antibodies was used to study the effects of chromium on protein tyrosine phosphorylation in intact H4 rat hepatoma cells. Treatment of cells with hexavalent chromium [Cr(VI)] was found to induce the tyrosine phosphorylation of three prominent sets of proteins, having median molecular masses of 210, 125, and 87 kDa. Cr(VI) pretreatment also inhibited the insulin-induced tyrosine phosphorylation of the major substrate of the insulin receptor kinase, insulin receptor substrate-1, and its subsequent association with the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3'-kinase. Furthermore, Cr(VI) was found to alter the pattern of other p85-binding (insulin-induced) phosphoproteins that were distributed throughout the soluble and particulate fractions of cells. Virtually all of the alterations in basal and insulin-induced phosphorylations associated with Cr(VI) treatment were also observed in cells treated with the protein kinase C (PKC) agonist phorbol-12-myristate-13-acetate. However, the effects of Cr(VI) were determined to be independent of PKC activity, because they were sustained in PKC-depleted cells. The pattern of phosphoproteins induced by Cr(VI) also had similarities to the pattern generated in response to the phosphatase inhibitor sodium orthovanadate. However, several specific differences, including the ability of vanadate to increase insulin receptor beta subunit autophosphorylation [i.e., an effect not observed with Cr(VI)], indicated that these agents modulate phosphorylation by distinct mechanisms. The ability of Cr(VI) to alter the phosphorylation state of key regulatory proteins in a manner similar to that of other biologically active agents suggests a mechanism by which this element can modulate the growth and metabolism of cells.
Mol Pharmacol 1995 Apr
PMID:Effects of chromium on basal and insulin-induced tyrosine phosphorylation in H4 hepatoma cells: comparison with phorbol-12-myristate-13-acetate and sodium orthovanadate. 753 87

Neutron activation study of elementary composition was performed on edible sea urchins Paracentrotus lividus from the National Park of Port-Cros. The analysis allows the identification and quantification of 22 elements: antimony, arsenic, baryum, bromine, cerium, chromium, cesium, cobalt, gold, iron, lanthane, potassium, sodium, rubidium, samarium, scandium, selenium, silver, strontium, thorium, uranium and zinc. The concentration levels were higher in the soft organic parts (alimentary canals and gonads) for all the elements, except for strontium, which developed a strong affinity with calcareous hard parts (tests, spines, masticating apparatus). We also found high rates of baryum, arsenic, zinc, bromine and iron. The hypothesis on the origin of these elements is discussed. The data obtained on this referential zone will soon be used to appreciate the perturbation of the elementary composition of urchins by pollution in various parts of the French seashore.
Cell Mol Biol (Noisy-le-grand) 1995 Jun
PMID:Neutron activation study of the natural elementary composition of edible sea urchins (Paracentrotus lividus Lamarck) in the National Park of Port-Cros (Mediterranean, France). 754 89

The involvement of reactive oxygen species in chromate-induced genotoxicity has been postulated. Because intracellular antioxidants help in eliminating the reactive species of oxygen, we have investigated both the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells exposed to nontoxic levels of chromium(VI) in culture. The cells treated with 0-->200 microM potassium chromate in a salts/glucose medium for 2 h were found to contain significantly lower levels of both small molecular weight and macromolecular antioxidants. In particular, the levels of glutathione and ascorbate were found to decrease with increased doses of chromate exposure in a dose-dependent manner. As little as 10 microM chromate was found to decrease these small molecular weight antioxidants significantly (p < 0.01). The macromolecular antioxidants, such as glutathione peroxidase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase were also significantly (p < 0.01) decreased by exposing the cells to as little as 10 microM chromate. Concomitantly, there was a dose-dependent increase in intracellular H2O2 accumulation in cells exposed to chromium(VI). These results indicate that chromate-induced genotoxicity may be due, at least in part, to decreased levels of intracellular antioxidants in conjunction with an increased production of the reactive oxygen species.
Mol Cell Biochem 1995 Jan 12
PMID:Alterations in the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells treated with potassium chromate. 775 43

The parallel fiber "en passant" synaptic endings of mouse cerebellar molecular layer have shown by means of transmission electron microscopy, the presence of an electron dense extravesicular material in samples perfused with Alcian blue. This alcianophilic material was digested in cerebellar tissue previously treated with testicular hyaluronidase, suggesting the presence of hyaluronic acid or chondroitin 4- or 6-sulphate. Freeze-fractured Rhesus monkey cerebellar cortex prepared for conventional scanning electron microscopy also revealed the presence in fractured synaptic varicosities of parallel fibers of a high mass density material, in which the synaptic vesicles are embedded. Examination of cryofractured primate cerebellar cortex coated with thin chromium films, 1-2 nm thick, in the high resolution field emission scanning electron microscope showed the SE-I topographic contrast of an extravesicular material deposited in axoplasmic matrix of fractured parallel synaptic endings. The precise localization of this material corresponds to that observed in transmission electron microscopy and conventional freeze-fracture scanning electron microscopy. These electron microscopic findings tend to agree with the omnipresence in several vertebrates of a presynaptic axoplasmic material, which seems to be proteoglycan in nature.
Cell Mol Biol (Noisy-le-grand) 1994 Sep
PMID:Proteoglycan ultracytochemistry and conventional and high resolution scanning electron microscopy of vertebrate cerebellar parallel fiber presynaptic endings. 781 87

This paper provides an exploration into the outer and inner surfaces of primate cerebellar neurons using secondary electron-I (SE-I) topographic contrast. SE-I enriched, chromium coated, cryofractured cerebellum staged within the condenser/objective lens stage of SEMs, equipped with high brightness LaB6 and field emission emitter, generated quality images of intact and fractured nerve cells studied at intermediate and high magnifications. Granule and Golgi cell surfaces revealed smooth, accurately delineated profiles of the true cell surface features, which lacked the SE-III dominated brilliance of conventional gold or gold-palladium decorated images. Fractured non synaptic segments of parallel fibers in the molecular layer showed interconnected anastomotic networks of ER tubules, vesicles and cisterns, whereas cross fractured presynaptic "en passant" endings of these fibers exhibited spheroidal synaptic vesicles and SE-I edge brightness contrast delineated their limiting plasma membranes. Parallel fiber fractured synaptic endings showed a homogeneous extravesicular material surrounding the synaptic vesicles. The neuroglial cytoplasm ensheathing nerve processes exhibited a smooth discontinuous surface. The high mass density surface of the myelin sheath showed a mixed population of globular structures, 10-30 nm, corresponding to protein and phospholipid microdomains.
Cell Mol Biol (Noisy-le-grand) 1994 Dec
PMID:High resolution (SE-I) scanning electron microscopy features of primate cerebellar cortex. 787 89


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