Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The LEC rat is a mutant inbred strain isolated from Long-Evans rats, which spontaneously develops hepatitis and hepatoma with high frequency. In this study, copper profiles of LEC rats, including copper concentration in the liver and concentrations of copper and ceruloplasmin in the serum, were investigated. It was found that copper accumulated in the liver of LEC rats immediately prior to the onset of hepatitis with a concentration of more than 50 times that of normal LEA rats, and serum concentrations of copper and ceruloplasmin decreased markedly, which resembled biochemically characteristic features of human Wilson's disease. Administration of d-penicillamine (100 mg/Kg/day p. o), a chelating agent, reduced the hepatic copper level and completely inhibited the development of hepatitis in LEC rats. Copper also accumulated in both cancerous and non-cancerous liver tissues of three 29-month old male LEC rats which had spontaneously developed hepatocellular carcinomas. These findings suggest that the hepatitis in LEC rats is caused by copper toxicity, and that the abnormal copper metabolism may be involved in hepatic carcinogenesis in the LEC rats. Therefore, it is considered that the LEC rat will provide a promising animal model for not only elucidating the pathogenesis of Wilson's disease and developing treatment strategies of the disease, but also for studying the role of copper in hepatic carcinogenesis.
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PMID:[Abnormal hepatic copper accumulation and its significance in LEC rats developing spontaneous hepatitis and hepatoma]. 195 41

Rats were injected 21 mg/kg dimethylhydrazine (DMH), in a single dose, subcutaneously (experimental run I), or 5 times at weekly intervals (experimental run II) to measure free-radical process indices in blood serum, liver and large bowel 24 hr after a single exposure and 6 months after 5 exposures. Run I identified marked DMH inhibition of blood-serum level of active forms of oxygen (AFO). However it did not involve any changes in the concentrations of such products of lipids peroxidation (LP) as dien conjugates, Schiff's bases and protein peroxides (PP). Neither did total antioxidation activity (TAA) or that of Cu, Zn-superoxydismutase (SOD) change. However, nitrite levels increased while those of ceruloplasmin decreased significantly. AFO levels also dropped in the liver, following a single injection of DMH, with TAA and SOD activity decreased significantly. No changes were observed in AFO generation processes in the bowel which was targeted by DMH treatment. A slight decrease in TAA, a rise in PP and diverse changes in the enzymatic system of antioxodation protection were recorded: decreased SOD activity and an insignificant rise in catalase level (like in the liver). Run II showed an intensification of peroxidation in blood serum and bowel in animals bearing intestinal tumors. However, no distinct changes occurred in the liver. The results point to a tendency of free-radical processes being intensified during DMH-induced carcinogenesis in rats.
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PMID:[Free-radical processes in blood serum, liver and large bowel during 1,2-dimethylhydrazine-induced carcinogenesis in rats]. 947 64

It has been suggested that high iron stores enhance colon carcinogenesis. The effect of high dietary iron (Fe) on indices of iron, copper (Cu) and manganese (Mn) status, lipid peroxidation using the thiobarbituric acid reactive substances assay, superoxide dismutase, glutathione peroxidase, glutathione transferase and ceruloplasmin activities, cell proliferation and development of preneoplastic lesions known as aberrant crypt foci (ACF) in rat colon was examined using a 3 x 2 factorial design. Male weanling Sprague-Dawley rats were fed adequate (AFe; 45 mg Fe/kg diet), moderately high (MHFe; 225 mg Fe/kg diet) and high (HFe; 450 mg Fe/kg diet) dietary Fe for 2.5 wk, then treated with azoxymethane (AOM; 2 injections, 1 wk apart; total dose 30 mg/kg body weight) or saline (n = 14-15 per group). Dietary treatment continued for another 6 wk after the second AOM dose. At the time of AOM injection, colon Fe concentrations were one- and threefold higher for MHFe and HFe rats, respectively, than for AFe rats. It was proposed that high dietary Fe would adversely affect Cu and Mn status, resulting in impaired antioxidant enzyme activity. However, neither indices of Cu and Mn status nor colonic mucosal antioxidant enzyme activities were affected by dietary Fe except for plasma ceruloplasmin activity, which was slightly lower in rats fed high iron diets than in rats fed adequate iron diets (P < 0.01). Dietary Fe had no significant effect on colonic mucosal lipid peroxidation, cell proliferation or ACF development. In conclusion, our findings suggest that dietary Fe concentrations that are approximately 5 and 10 times adequate do not enhance oxidative stress, cell proliferation and ACF development in the colon of rats.
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PMID:Iron supplementation does not affect cell proliferation or aberrant crypt foci development in the colon of sprague-dawley rats. 952 41

Variations in copper-containing superoxide dismutase (SOD) 1 are hypothesized to produce variations in resistance to carcinogenesis, particularly in mammary tissue. Therefore, it is reasonable to speculate that low copper intake, which causes low SOD 1 activities in various tissues, would cause poor resistance to mammary carcinogenesis. This idea was tested using female rats fed diets either low or adequate in copper (< 0.5 or 8 mg copper/kg diet) plus or minus oral gavage with the mammary carcinogen 7,12-dimethylbenz[a]anthracene (5 mg/kg, given 5 wk after dietary modification, 28 wk before sacrifice). Low copper intake produced low activities of two serum copper enzymes: ceruloplasmin and extracellular SOD. In contrast, low copper intake did not affect mammary tissue SOD 1 activities, nor did it statistically influence any of several parameters of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis.
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PMID:No effects of low copper intake on rat mammary tissue superoxide dismutase 1 activity and mammary chemical carcinogenesis. 979 75

We previously demonstrated that rats exposed to the peroxisome proliferator (PP) diethylhexylphthalate (DEHP) had reduced serum ceruloplasmin (CP) oxidase activity, which suggests tissue copper deposition. Copper is highly toxic in excess, and results in cellular damage and hepatocellular carcinomas (HCC). This study addresses changes in expression of copper-related genes and metal accumulation in hyperplastic liver and tumors induced by PP. Male rats were fed diets containing DEHP or clofibrate (CLF) for 3-60 days (hyperplasia) and 4-chloro-6-(2,3 xylidino)-2-pyrimidinyl-thio(N-beta-hydroxyethyl) acetamide for 10 months (HCC). During hyperplasia, an immediate and progressive decrease in serum CP activity was observed (P < 0.05), as were reductions in mRNA levels for both CP and Wilson's disease gene (WD gene, a P-type ATPase) (P < 0.05). Tumor-bearing rats had lower serum CP activity (P < 0.05), and CP and WD gene mRNA levels were reduced in tumors (P < 0.05), and in liver surrounding tumors (SL) (P < 0.05). Metallothionein mRNA showed no consistent changes during hyperplasia. Tumors showed a 2.5-fold induction of metallothionein mRNA (P < 0.05), and a 1.2-fold increase in SL. Temporal increases in liver copper content occurred during hyperplasia, with increases of 2-fold (DEHP) and 3.3-fold (CLF) at 60 days (P < 0.05). Copper content was 2.2-fold higher in tumors (P < 0.05) and 1.7-fold higher in SL; iron did not increase and zinc decreased temporally. Thus, copper accumulation and changes in copper-related gene expression may be contributing factors in liver neoplasia in PP-treated rats. Loss of CP results in decreased free radical scavenger capacity and thus may enhance oxidative damage induced by PPs.
Carcinogenesis 1999 Jun
PMID:Hepatic hyperplasia and cancer in rats: alterations in copper metabolism. 1035 93

The expression of lactoferrin (LF), ceruloplasmin (CP) and secretory component (SC) in various thyroid diseases was investigated using an immunohistochemical method. LF is an iron-binding protein overexpressed in certain human adenocarcinomas. CP is implicated in carcinogenesis and SC is part of the local immune defense system. Sections of 15 follicular adenomas, 5 follicular carcinomas (FC), 16 papillary carcinomas (PC), 15 goitres and 2 cases of lymphocytic thyroiditis were re-examined and investigated immunohistologically by a streptavidin-biotin method. A positive immunostain reaction for CP and LF was observed in all cases of PC and FC. A positive immunostain reaction for SC was observed in 13/16 cases of PC and 4/5 cases of FC. A negative immunostain reaction for CP, LF and SC was observed in medullary cancers, in follicular adenomas and in the cases with goitre. We conclude that the immunostain expression of LF, CP and SC is a valuable diagnostic aid in the differential diagnosis between benign and malignant thyroid tumors. The expression of SC indicates the presence of a local immunodefensive system.
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PMID:Immunohistochemical study of ceruloplasmin, lactoferrin and secretory component expression in neoplastic and non-neoplastic thyroid gland diseases. 1185 89

Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western-blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins.
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PMID:Nitrated and oxidized plasma proteins in smokers and lung cancer patients. 1121 82

A balance between oxidant carcinogens and endogenous antioxidant defence is of particular relevance to the carcinogenesis. Ceruloplasmin (Cp) carries up to 90% of Cu in plasma and performs ferroxidase, antioxidant and amine oxidase activity. Cu and Zn, as trace elements, have been recognized to play an important role as cofactors of SOD. The study presents the relationship of the Cp oxidase activity and concentrations of Cu and Zn in serum of 62 patients with breast (BCA), lung (LCA), gastrointestinal (GICA) and gynecological (GYNCA) cancer. The Cp oxidase activity was determined in serum with o-dianisidine as a substrate. Cu and Zn concentrations in serum were measured by using atomic absorption spectrometry. The results of the study have shown significant increase in the mean serum Cp oxidase activity and total Cu concentrations in all patient groups compared with the control one. The total mean serum Zn concentration was found to be decreased only in LCA group as compared with the control. The effect of the cancer progress on the Cp oxidase activity and concentrations of Cu and Zn was observed within the group of all cancer patients (ALLCA) and within the GICA group. The only significant difference in Cu concentrations among various stages of the disease was observed in GICA between local and distant one. Significant positive correlation coefficients were caLculated for the Cp activity and Cu concentrations in the control group and all patients groups, also according to the cancer progress. Future research is needed to evaLuate the consequences of the elevation of the serum Cp oxidase activity and concentration of Cp, Cu and Zn for the host antioxidant-oxidant balance.
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PMID:Oxidase activity of ceruloplasmin and concentrations of copper and zinc in serum of cancer patients. 1178 88

Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects.
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PMID:Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study. 1885 Jan 83

To identify differentially regulated molecules related to early and late stages of tumor promotion in a rat two-stage thyroid carcinogenesis model by an antithyroid agent, sulfadimethoxine, microarray-based microdissected lesion-specific gene expression profiling was carried out. Proliferative lesions for profiling were divided into two categories: (i) focal follicular cell hyperplasias (FFCH) and adenomas (Ad) as early lesions; and (ii) carcinomas (Ca) as more advanced. In both cases, gene expression was compared with that in surrounding non-tumor follicular cells. Characteristically, upregulation of cell cycle-related genes in FFCH + Ad, downregulation of genes related to tumor suppression and transcription inhibitors of inhibitor of DNA binding (Id) family proteins in Ca, and upregulation of genes related to cell proliferation and tumor progression in common in FFCH + Ad and Ca, were detected. The immunohistochemical distributions of molecules included in the altered expression profiles were further examined. In parallel with microarray data, increased localization of ceruloplasmin, cyclin B1, and cell division cycle 2 homolog A, and decreased localization of poliovirus receptor-related 3 and Id3 were observed in all types of lesion. Although inconsistent with the microarray data, thyroglobulin immunoreactivity appeared to reduce in Ca. The results thus suggest cell cycling facilitation by induction of M-phase-promoting factor consisting of cyclin B1 and cell division cycle 2 homolog A and generation of oxidative responses as evidenced by ceruloplasmin accumulation from an early stage, as well as suppression of cell adhesion involving poliovirus receptor-related 3 and inhibition of cellular differentiation regulated by Id3. Decrease of thyroglobulin in Ca may reflect dedifferentiation with progression.
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PMID:Cellular distributions of molecules with altered expression specific to thyroid proliferative lesions developing in a rat thyroid carcinogenesis model. 1929 5


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