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

The relative activities of neutral, cationic, and anionic chromium ascorbate complexes toward isolated human mitochondrial and genomic DNA were investigated at physiologically relevant conditions by agarose gel electrophoresis. A direct relationship between the charge of the Cr(III) species and their DNA-damaging properties was found. The cationic species were found to be fully capable of DNA-cleavage, even in short incubation periods. Incubations were also performed in the presence of amino acids. No apparent effect was observed under the applied experimental conditions to facilitate or prevent damage through the ternary amino acid-Cr-DNA adduct formation or binary chromium-amino acid complex formation.
J Biochem Mol Biol 2003 Jul 31
PMID:Effects of neutral, cationic, and anionic chromium ascorbate complexes on isolated human mitochondrial and genomic DNA. 1289

Chromium containing mica is called fuchsite. Fuchsite originating from the Nellore district of India containing 3.37 wt.% of chromium is used in the present study. Optical absorption and EPR studies were carried out at room temperature (RT). The optical absorption spectrum gives energies at 14925, 15070, 15715, 16400, 17730 and 21740 cm(-1), which are attributed to spin-allowed transitions for Cr(3+) in an octahedral symmetry. EPR spectra show a strong resonance with g=1.98 along with two sets of weak resonances which are attributed to two sets of chromium in the sample. The zero field splitting parameter (D) is almost zero. These spectra are due to Cr(3+) in the mineral. The NIR spectrum is due to hydroxyl ions in the sample.
Spectrochim Acta A Mol Biomol Spectrosc 2003 Sep
PMID:Optical absorption and EPR spectra of fuchsite. 1296 57

Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.
Mol Cell Biochem 2003 Oct
PMID:Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats. 1457 12

Earlier studies from our laboratory have indicated insulin sensitizing action of chromium picolinate as the mechanism of its anti-diabetic activity in experimental models of type I and type II diabetes. In the present investigation, we have evaluated the effects of chronic administration of chromium picolinate on the functional and histological alterations of streptozotocin (STZ)-induced diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40 mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal injection of STZ (90 mg/kg) in 2-day old rat pups which in adulthood develop abnormalities resembling type II diabetes. Chromium picolinate was administered at 8 microg/ml in drinking water for 6 weeks and was found to improve glucose tolerance and increase insulin sensitivity of STZ-diabetic rats. This treatment decrease elevated serum creatinine and urea levels as well as elevated serum levels of hepatic enzymes of both groups of diabetic rats. Histopathological studies of kidney and liver show decrease in the intensity and incidence of vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not alter the normal function or morphology of control rats. Chronic chromium picolinate at the therapeutic doses that improved glucose tolerance, was observed to have no hepatotoxic or nephrotoxic potential. It was rather found to improve renal and hepatic function and to reduce abnormalities associated with STZ-diabetes. Chromium picolinate could play an important role in the long term management of diabetes mellitus.
J Cell Mol Med
PMID:Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats. 1459 57

Hexavalent chromium (Cr(VI)) compounds are widely accepted as human lung carcinogens. However, there have been few investigations of the genotoxicity of Cr(VI) in human lung cells. Moreover, our knowledge of the effects of Cr(VI) in human lung cells is further limited because the available data generally focus on the effects of only lead chromate (PbCrO(4)) and sodium chromate (Na(2)CrO(4)). To fully understand these carcinogenic compounds, the genotoxic effects to its target cells need to be evaluated for additional Cr(VI) salts. Accordingly, we investigated the cytotoxicity and clastogenicity of barium chromate (BC) in a human lung cell culture model (WTHBF-6 cells). We found that BC induced concentration-dependent cytotoxicity in WTHBF-6 cells, with relative survival of 88%, 74%, 67%, 12%, 3%, and 0.1% after exposure to 0.01, 0.05, 0.1, 0.5, 1, and 5 microg/cm(2) BC, respectively. Similarly, the amount of chromosomal damage also increased with concentration after a 24-h exposure. Specifically, 0.01, 0.05, 0.1, and 0.5 microg/cm(2) BaCrO(4) damaged 5%, 9%, 22%, and 49% of metaphase cells, with the total damage reaching 5, 10, 28, and 65 aberrations per 100 metaphases, respectively. Concentrations of 1 and 5 microg/cm(2) BC induced a profound cell cycle delay, and no metaphases were observed. The spectrum of damage included chromatid and chromosome-type lesions consistent with mechanistic events associated with the activation of oncogenes and inactivation of tumor suppressor genes. Overall the data indicate that BC is cytotoxic and genotoxic to human lung cells.
Environ Mol Mutagen 2003
PMID:Barium chromate is cytotoxic and genotoxic to human lung cells. 1467 72

Stress response of yeast Candida intermedia ZIM 156 exposed to chromium(VI) was investigated. Yeast cells were treated with Cr(VI) in concentrations of 50, 100, 300 and 500 microM in the mid-exponential growth phase. Monitoring of some bioprocess parameters during growth, specifically pO(2), showed that Cr(VI) addition, specifically in concentration of 100 and partially 50 micromol/L, increased metabolism intensity, which is connected to induced stress responses. Furthermore, oxidation of 2',7'-dichlorofluorescin indicated increased intracellular oxidant level, specifically at 100 microM Cr(VI) concentration. Antioxidant defense systems were further investigated. Catalase and superoxide dismutase activity was not increased in the cells exposed to the both Cr(VI) concentrations, which indicate that catalase and superoxide dismutase do not participate in cell defense systems. In contrast intracellular glutathione content in reduced form increased significantly in the cells exposed to 100 micromol Cr(VI)/L. Therefore, we demonstrated that glutathione plays an important role in the stress response of C. intermedia to Cr(VI).
J Biochem Mol Toxicol 2003
PMID:Stress response of yeast candida intermedia to Cr(VI). 1470 86

Hexavalent chromium (Cr(VI)) is a metal of increasing public health concern, as exposure to it is widespread and it is a well-established cause of human bronchial carcinomas and fibrosarcomas. The water-insoluble Cr(VI) salts are potent carcinogens compared to the water soluble salts; yet the genotoxic mechanisms of both may be mediated by soluble Cr(VI) ions. Currently, these mechanisms are poorly understood. Emerging evidence suggests that initial cell culture models used to study the general toxicity of Cr(VI) may be suboptimal for investigating mechanisms specific to human bronchial cells. Accordingly, we have developed a new model system of human bronchial cells by introducing hTERT, the catalytic subunit of human telomerase, into primary human bronchial fibroblasts (PHBF). We have isolated a stable, clonally derived cell line, WHTBF-6, that demonstrate reconstitution of telomerase activity and maintenance of telomere lengths with increasing culture age. WHTBF-6 has been characterized as having an extended in vitro lifespan, a normal growth rate, a normal diploid karyotype that is maintained over time, and exhibits serum-dependent contact-inhibited anchorage-dependent growth. Moreover, we find that both particulate and soluble hexavalent chromium induce a pattern and degree of cytotoxicity and clastogenicity in WHTBF-6 that is similar to the parental PHBF cells. Because telomerase does not compromise growth or the response to Cr(VI), our results indicate that this is an excellent system for studying the mechanisms of Cr(VI) and potentially other carcinogens implicated in the development of lung cancer.
Mol Cell Biochem 2004 Jan
PMID:Telomerase-mediated lifespan extension of human bronchial cells does not affect hexavalent chromium-induced cytotoxicity or genotoxicity. 1497 51

Cell proliferation and apoptosis are controlled by tightly orchestrated signaling pathways that culminate in transcriptional activation/repression of multiple proteins. Dysregulation of cell cycle and/or apoptosis control may lead to genomic instability, neoplastic transformation and tumor progression. Under certain conditions, some hexavalent chromium [Cr(VI)] compounds are toxic and carcinogenic in the human respiratory tract, and we have shown that they induce apoptosis and/or cell cycle arrest in a p53-dependent fashion. There is increasing evidence linking extracellular signal-regulated kinase (ERK) activation with the DNA damage response, by both p53-dependent and -independent mechanisms. Here, the aim was to study the effect of Cr(VI) transcriptional regulation of key cell cycle inhibitors and pro- and anti-apoptotic proteins, as well as the role of ERK activation in the Cr(VI) genotoxic response. Diploid human lung fibroblasts were incubated with 3-9 uM Na2CrO4, and RNA was isolated at 4, 8, and 24 h, as well as 24 h after Cr(VI) exposure was terminated (recovery). mRNA expression was quantitated by RNase protection assay with a 32P-labeled multi-transcript probe containing gene sequences for the cdk inhibitors, p21waf1/cip1, p27kip1, p16INK4a, p15INK4b; the pro-apoptotic proteins bcl-XS and bax; the anti-apoptotic proteins bcl-W, bcl-XL, and bcl2, GADD45, and cyclin A. In general, bcl-W and bcl-XL expression were both downregulated after Cr exposure, to around 50% at 24 h, which was more pronounced after the recovery period. At Cr(VI) concentrations < or = 6 uM, bcl2 expression was upregulated. Of particular interest is that bax expression was reduced, in a dose and time-dependent fashion, however that of bcl-XS was elevated by nearly 3-fold after 8 h, and declined to control levels at the end of the recovery period. Expression of GADD45 and p21 were both upregulated by 2-fold at 8 h, but declined to control levels during recovery. Neither the expression of p27 nor that of p16 were apparently affected by Cr(VI) exposure, however the expression of p15 was markedly increased after exposure to all concentrations of Cr(VI). Finally, the expression of cyclin A was decreased after 24 h Cr(VI) exposure. Cr(VI) induced a transient burst of ERK activity (2-6-fold over control) around 0.5-3 h after exposure. However, inhibition of ERK activation with PD98059 had no effect on the Cr-induced alterations in gene expression. Moreover, Cr(VI)-induced clonogenic lethality, as assessed after 24 h exposure to 1 and 2 uM Cr(VI), was also not affected by ERK inhibition. These data suggest that both p53-dependent and -independent apoptotic and growth-inhibitory pathways are markedly affected by Cr(VI) exposure. However, the ability of Cr(VI) to affect key apoptotic and growth arresting genes, and thus clonogenic lethality, appears to be independent of ERK. Continued investigation into the cellular and molecular mechanisms of Cr(VI)-induced cell cycle and apoptosis control should further the understanding of Cr(VI)-associated carcinogenesis.
Mol Cell Biochem 2004 Jan
PMID:Induction of pro-apoptotic and cell cycle-inhibiting genes in chromium (VI)-treated human lung fibroblasts: lack of effect of ERK. 1497 55

Chromium(VI) (Cr(VI)) can suppress both DNA replication and transcription as a result of chromium (Cr)-induced DNA damage. While progress has been made in the characterization of Cr-induced DNA polymerase arresting lesions, very little information is available on the inhibition of transcription by this metal. The aim of the present study was to identify the molecular mechanisms involved in the reduction of RNA synthesis by Cr. Following treatment with a moderately cytotoxic dose (approximately LC50) of Cr(VI) (150 microM for 2 h), total RNA synthesis was initially suppressed in CHO cells and recovered to control levels within 72 h post-treatment. In vitro nuclear run-on transcription assays of nuclei isolated from Cr(VI)-treated cells showed a similar amount of RNA synthesis suppression as observed in intact cells. Qualitative analysis of nascent transcripts revealed a general, concentration-dependent reduction in size suggesting that transcriptional elongation was inhibited following Cr-treatment. Transcriptional initiation in these nuclei was also reduced. To better determine whether transcriptional suppression was related to Cr-induced DNA damage we examined the transcriptional activity of T7 RNA polymerase on Cr(III)-treated plasmid DNA. Treatment of pGEM3Z-TS DNA with Cr(III) resulted in transcriptional arrest which occurred primarily at GC-rich and palindromic regions. However, in contrast to the cellular data, transcriptional initiation was unaffected in the in vitro transcription arrest assays. Taken together, these results suggest that the suppression of RNA synthesis by Cr is related to chromium-induced template DNA damage which prevents elongation leading to premature RNA polymerase arrest.
Mol Cell Biochem 2004 Jan
PMID:Mechanisms of chromium-induced suppression of RNA synthesis in cellular and cell-free systems: relationship to RNA polymerase arrest. 1497 56

Exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as lead chromate (PbCrO4), has been associated with lung cancer and respiratory tract toxicity. Previous studies indicate that the solubility of Cr(VI)-compounds is an important factor in Cr(VI)-induced carcinogenesis. The present study investigates reactive oxygen species (ROS) generation by PbCrO4 particles and cellular responses using RAW 264.7 cells. A mixture containing PbCrO4 and RAW 264.7 cells generated hydroxyl radical ((.)OH), using cellularly generated H2O2 as a precursor, as measured by electron spin resonance (ESR) spin trapping in combination with H2O2 and (.)OH scavengers, catalase and sodium formate. The effect of ascorbic acid on (.)OH radicals was also measured using ESR. Confocal microscopy showed that particles could become either bound to the cell surface or engulfed over a 120 min time period. H2O2 generation and O2 consumption were also increased after treatment of the cells with PbCrO4. Both NF-kappaB and AP-1 were activated after exposure to PbCrO4 particles as measured by the NF-kappaB or AP-1 luciferase reporter plasmid assay. Our investigation thus demonstrated that the RAW 264.7 cells phagocytized the PbCrO4 particles leading to accumulation of the particles within vacuoles in the cytoplasm. These particles could induce chronic production of ROS and activation of NF-kappaB and AP-1. Such induction of transcription pathways may be involved in the inflammatory and carcinogenic responses induced by Cr(VI)-containing particles.
Mol Cell Biochem 2004 Jan
PMID:PbCrO4 mediates cellular responses via reactive oxygen species. 1497 58


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