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

The concentration-dependent effects of chromium picolinate and chromium nicotinate were assessed on the enhanced production of reactive oxygen species including superoxide anion and hydroxyl radicals, and lipid peroxidation and DNA fragmentation in cultured macrophage J774A.1 cells. The macrophage cells were incubated with 0-50 micrograms/ml [corrected] concentrations of these chromium (III) salts for 0 and 24 hrs at 37 degrees C. Concentration-dependent effects were observed. Lipid peroxidation increased by 1.3-1.5-fold following treatment of these cells with chromium picolinate while at these same concentrations of chromium nicotinate approximately 1.2-1.8-fold increases in lipid peroxidation were observed. Increases of 1.0-1.5-fold occurred in the production of superoxide anion as determined by cytochrome c reduction following treatment with chromium picolinate while with these same concentrations and conditions only 1.1-1.2-fold increases in cytochrome c reduction were observed following treatment with chromium nicotinate. Approximately 1.2-1.5-fold increases in hydroxyl radical production were observed following treatment of these macrophage cells with increasing concentrations of chromium picolinate and chromium nicotinate. Incubation of the cells with 30-50 micrograms/ml concentrations of chromium picolinate produced 1.2-1.6 fold increases in DNA fragmentation, while under these same conditions with chromium nicotinate 1.2-1.3-fold increases in DNA fragmentation occurred. No significant loss in cell viability was observed with either chromium salt. These results demonstrate that incubation of macrophage J774A.1 cells with these chromium salts induces low levels of oxidative stress as demonstrated by the biochemical assay techniques employed in this study.
Res Commun Mol Pathol Pharmacol 1997 Sep
PMID:Comparative induction of oxidative stress in cultured J774A.1 macrophage cells by chromium picolinate and chromium nicotinate. 938 93

The isotope dilution technique of [6-3H]glucose, [U-14C]lactate and [l-14C]propionate was used to evaluate the effect of dietary chromium (Cr) supplementation on whole-body kinetics of glucose, lactate, and propionate in rams. Rams were fed a high grain diet at 2% of body weight with or without 0.5 ppm of supplemental Cr from chelated Cr for the initial 14 days, and then intake was increased to 2.5% at body weight for the last 9 days. Weight gain was enhanced (P < 0.01) with Cr supplementation. Plasma concentrations of glucose, lactate, and propionate were not influenced by Cr supplementation. Turnover rates of glucose and lactate, and their interconversion were also not influenced. Propionate turnover rate tended to increase (P = 0.11) and the conversion of propionate to glucose increased (P < 0.05) with Cr supplementation, leading the increased proportional contribution of propionate to glucose turnover rate (P < 0.05). Chromium supplementation may influence the contribution of each glucogenic substrate for glucose production in rams fed a high grain diet.
Comp Biochem Physiol B Biochem Mol Biol 1997 Sep
PMID:Effect of supplemental chromium on whole-body kinetics of glucose, lactate, and propionate in rams fed a high grain diet. 941

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).
Biochem Mol Biol Int 1998 Oct
PMID:Chromium levels in patients with internal diseases. 980 4

We have previously shown that trivalent chromium, and hexavalent chromium in the presence of one of its primary in vivo reductants, ascorbate, can bind to DNA and form interstrand crosslinks capable of obstructing replication. This effect was demonstrated in vitro by using Sequenase Version 2.0 T7 DNA polymerase; its parent enzyme, the unmodified T7 DNA polymerase; and Escherichia coli polymerase I large (Klenow) fragment; and it was demonstrated ex vivo by using Taq polymerase and DNA from chromium-treated human lung cells as template. This study was performed to determine whether DNA-bound chromium affects mammalian DNA polymerases in the same manner. Two mammalian enzymes, DNA polymerase alpha and DNA polymerase beta, were used. DNA polymerase alpha is a processive enzyme believed to be the primary lagging-stand synthetase, whereas DNA polymerase beta is a non-processive enzyme believed to function in DNA repair by filling single stranded gaps one base at a time. DNA polymerase arrest assays were performed with each of these enzymes to replicate DNA with toxicologically relevant levels of chromium adducts produced by either trivalent chromium or hexavalent chromium and ascorbate. Both enzymes responded to chromium-DNA damage by arresting replication, and the arrests increased in a dose-dependent manner. Furthermore, the guanine-specific pattern of arrests produced when an exonuclease-free preparation of DNA polymerase beta was used corresponded exactly to the arrest patterns produced in vitro by the exonuclease-free enzyme Sequenase and ex vivo by Taq polymerase. These results suggest that replication arrest may be a common response of polymerases to DNA-chromium lesions and provide a plausible mechanism for the inhibition of DNA synthesis and S-phase cell-cycle delay that occurs in mammalian cells treated with genotoxic chromium compounds.
Mol Carcinog 1998 Dec
PMID:Arrest of replication by mammalian DNA polymerases alpha and beta caused by chromium-DNA lesions. 986 48

Due to high temperature factors and the lack of considerable electron density, electron microscopy and X-ray experiments on the cytoplasmic E-F loop of bacteriorhodopsin result in a variety of structural models. As the experimental conditions regarding ionic strength, temperature and the presence of detergents may affect the structure of the E-F loop, we employ electron paramagnetic resonance and site-directed spin-labeling to study the structure of this loop under physiological conditions. The amino acid residues at positions 154 to 171 were replaced by cysteine residues and derivatized with a sulfhydryl-specific nitroxide spin label one by one. The conventional and power saturation electron paramagnetic spectroscopy provide the mobility of the nitroxide and its accessibility to dissolved molecular oxygen and membrane-impermeable chromium oxalate in the respective site. The results show that K159 and A168 are located at the water-lipid interface of helices E and F, respectively. The orientation of the amino acid side-chains in the helical regions from positions 154 to 159 and 166 to 171 were found to agree with published structural data for bacteriorhodopsin. In the residue sequence from positions 160 to 165 the EPR data yield evidence for a turned loop structure with the side-chains of M163 and S162 oriented towards the proton channel and the water phase, respectively.
J Mol Biol 1999 Mar 19
PMID:Site-directed spin-labeling reveals the orientation of the amino acid side-chains in the E-F loop of bacteriorhodopsin. 1007 14

The cellular response to multiple carcinogen treatment has not been extensively studied, even though the effect of individual carcinogens is, in many cases, well known. We have previously shown that potassium dichromate can protect normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide (BPDE), and that this effect may be via an oxidative stress mechanism [Tesfai et al. (1998) Mutat Res 416:159-168]. Here, we extend our previous work by showing that nickel subsulfide can produce the some effect. Normal human fibroblasts, preincubated with nickel subsulfide for 46 hr followed by a coincubation of nickel subsulfide and BPDE for 2 hr, showed a dramatic reduction in the mutant frequency of the hypoxanthine (guanine)phosphoribosyl-transferase (HPRT) gene when compared to cells treated only with BPDE. The preincubation period with nickel subsulfide was necessary to see the antagonistic effect, since it was not observed if the cells were simply incubated with both carcinogens for 2 hr. The extent of the antagonistic effect was nickel subsulfide dose-dependent and also appeared to be species-specific, since the effect was not observed when Chinese hamster fibroblasts were tested. Finally, the antagonistic effect of the nickel subsulfide was eliminated by vitamin E, suggesting that production of reactive oxygen species by the nickel may be required. This data, along with our previous work, suggest that the antagonistic effect we observe is not chromium-specific, and that it could be species-specific.
Environ Mol Mutagen 1999
PMID:Nickel subsulfide is similar to potassium dichromate in protecting normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide. 1033 23

An SV40-based shuttle vector, pZ189, was used to characterize the mutation specificity and to explore the mechanism of chromium mutagenesis in mammalian cells. We showed previously that mutagenic DNA damage is induced by the treatment of plasmid with chromium(VI) plus glutathione in vitro. The induced mutation pattern suggested that chromium mutagenesis can be induced by the generation of reactive oxygen intermediates. To further investigate the mechanism of chromium mutagenesis, we treated cultured mammalian cells containing normal pZ189 vector with chromium(VI). Mutations were induced by Cr(VI) in a dose-dependent manner. The majority of base substitution mutations were widely distributed across the supF mutation target gene and occurred mainly at GC basepairs. Overall, the mutation spectra were not significantly different from each other except for a mutation hot spot at position 43, observed only in plasmids from Cr(VI)-treated cells. The characteristics of Cr(VI)-induced mutations were similar to those observed in the mutation spectra induced by H2O2 treatment of the pZ189 plasmid or plasmid-containing cells. These results are consistent with the hypothesis that induction of mutations by chromium in cultured cells occurs through the generation of oxidative DNA damage.
Environ Mol Mutagen 1999
PMID:Mutational specificity in a shuttle vector replicating in chromium(VI)-treated mammalian cells. 1039 79

The toxic metals arsenic(III) and chromium(VI) are considered human carcinogens, although they may act through different mechanisms. We previously showed that when administered at single low, non-overtly toxic doses, chromium, arsenic, and several other chemical carcinogens preferentially alter expression of several model inducible genes in both whole-animal and cell-culture systems. In this study, we assessed whether chromium and arsenic target specific signaling pathways within cells to selectively modulate gene expression. We examined the effects of non-cytotoxic and cytotoxic doses of arsenic(III) and chromium(VI) on nuclear binding of the transcription factors AP-1, NF-kappaB, Sp1, and YB-1 in human MDA-MB-435 breast cancer and rat H4IIE hepatoma cells. These transcription factors were chosen because they may regulate many inducible genes, including those previously shown to be altered by metal treatments. We report that both arsenic and chromium significantly altered nuclear binding levels of these factors to their respective cis-acting elements. However, there were qualitative and quantitative differences in these effects that were dependent on the metal, time, dose, transcription factor, and cell line. These effects may play a significant role in metal-induced alterations in gene expression.
Mol Carcinog 1999 Jul
PMID:Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. 1041 Nov 48

Two chromium(VI) compounds (potassium chromate and potassium dichromate) and one chromium(III) compound, chromium chloride, were evaluated for genotoxic effects in the wing spot test of Drosophila melanogaster following standard procedures. This assay detects both somatic recombination and mutational events. The genotoxic effects were determined from the appearance of wing spots in flies transheterozygous for the third chromosome recessive markers multiple wing hairs (mwh) and flare-3 (flr(3)), as well as in flies heterozygous formwh and the multiply inverted TM3 balancer chromosome. Genetic changes induced in somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wingblade. Single spots are due to different genotoxic mechanisms: point mutation, deletion, chromosome breakage, and mitotic recombination; while twin spots are produced only by mitotic recombination. From our results it appears that both chromium(VI) compounds clearly increase the incidence of mutant clones by inducing high increases in the frequency of all types of clones recorded. On the contrary, chromium(III) did not increase the frequency of mutant clones. A high proportion of the total spot induction was due to mitotic recombination, confirming previously reported data on the strong recombinogenic activity of chromium(VI) compounds.
Environ Mol Mutagen 1999
PMID:Genotoxic activity of different chromium compounds in larval cells of Drosophila melanogaster, as measured in the wing spot test. 1046 23

DNA-protein crosslinks (DPCs) were induced in intact human leukemic T-lymphocyte MOLT4 cells or isolated nuclei by treatment with potassium chromate, chromium(III) chloride hexahydrate or x-rays. The proteins complexed to DNA were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis (PAGE). A group of identical non-histone proteins was crosslinked to DNA by any of the three treatments, except that a 51 kDa basic protein was additionally complexed to DNA when either potassium chromate or chromium(III) chloride hexahydrate was the crosslinking agent. Treatment of chromate-induced DNA-protein crosslinks with EDTA or thiourea followed by ultracentifugation dissociated the major proteins from the complex indicating that these proteins were crosslinked to DNA by direct participation of a EDTA-chelatable form of chromium such as Cr(III) through sulfur containing amino acid residues. The 51 kDa protein was not seen in the post-EDTA pellet but was present in the post-thiourea pellet, indicating that it was also crosslinked to DNA by Cr(III) through non-sulfur-containing amino acids. Digestion of x-rays-induced DPCs by DNase I also revealed this protein on two-dimensional gels indicating that the same protein was also crosslinked by oxidative mechanisms. The involvement of oxidative mechanisms in the crosslinking process was indicated as the majority of the proteins in chromate-induced DPCs were resistant to EDTA and thiourea treatment, and were found to crosslink to DNA when x-rays were used as the crosslinking agent. These results suggest that the chromate-induced DPCs are formed by the generation of reactive oxygen species during the intracellular chromate reduction as well as by the biologically generated Cr(III). About 19% of DNA-protein crosslinks actually involve Cr(III) crosslinking DNA to proteins, of which about 14% involve Cr(III) crosslinking DNA to proteins through non-sulfhydryl containing moieties and about 5% involve Cr(III) crosslinking DNA to sulfhydryl groups on proteins. The remaining 81% of DNA-protein crosslinks appear to be oxidatively crosslinked out of which about 45% appear to be through sulfhydryl groups and another 36% appear to be through non-sulfhydryl groups.
Mol Cell Biochem 1999 Sep
PMID:Analysis of EDTA-chelatable proteins from DNA-protein crosslinks induced by a carcinogenic chromium(VI) in cultured intact human cells. 1054 63


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