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

The plasma membrane of eukaryotic cells contains an NADH oxidase which can transfer electrons across the membrane. This oxidase is controlled by hormones, growth factors and other ligands which bind to receptors in the plasma membrane. Oncogenes also affect activity of the oxidase. Natural serum components such as diferric transferrin and ceruloplasmin which stimulate proliferation also stimulate membrane oxidase activity. Additional growth factors can be required to complement the proliferative effect. Electron transport across the plasma membrane can be measured by the reduction of impermeable electron acceptors, such as ferricyanide, which also stimulate cell growth. The oxidants activate growth-related signals such as cytosolic alkalinization and calcium mobilization. Antiproliferative agents such as adriamycin and retinoic acid inhibit the plasma membrane electron transport. Flavin, Coenzyme Q and an iron chelate on the cell surface are apparent electron carriers for the transmembrane electron transport. Coenzyme Q10 stimulates cell growth, and Coenzyme Q analogs such as capsaicin and chloroquine reversibly inhibit both growth and transmembrane electron transport. Addition of iron salts to the depleted cells restores activity and growth. The ligand-activated oxidase in the plasma membrane introduces a new basis for control of signal transduction in cells. The redox state of the quinone in the oxidase is proposed to control tyrosine kinase either by generation of H2O2 or redox-induced conformational change.
Mol Aspects Med 1994
PMID:Coenzyme Q10, plasma membrane oxidase and growth control. 775 19

Copper (Cu) and zinc (Zn)-binding superoxide dismutase (Cu,Zn-SOD) is synthesized always in a form of holo-protein in the liver of LEC rats, a genetically disordered mutant strain in Cu metabolism which accumulates Cu in a form bound to metallothionein (MT). On the other hand, ceruloplasmin (Cp) is synthesized in the liver and excreted into the blood plasma mostly as an apo-protein before the onset of acute hepatitis, and then holoform at the onset of jaundice. Thus, Cu is supplied differentially between Cp and SOD, and at different times, i.e., before and at the onset of acute hepatitis. Availability of Cu to apo-SOD was examined to explain the mechanisms for the differential supply of Cu among three different Cu forms; i) cuprous ion bound to glutathione, ii) free cupric ion, and iii) cuprous ion bound to MT. Cu was transferred to SOD from the three Cu complexes though MT-bound Cu was a less efficient Cu source to apo-SOD. The results indicate that SOD is always present in a holo-form in LEC rats because even MT-bound Cu can be supplied to SOD, while Cp is present in an apo-form because Cu is sequestered to MT and not available in free ionic forms in LEC rats before the onset of acute hepatitis.
Res Commun Mol Pathol Pharmacol 1994 Oct
PMID:Direct transfer of copper from metallothionein to superoxide dismutase: a possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats. 785 Feb 52

Xanthine oxidase exhibits ferroxidase activity and previously has been shown to catalyze the oxidative incorporation of iron into apotransferrin, the iron transport protein of plasma. These studies demonstrate that xanthine oxidase also efficiently promotes the oxidative incorporation of iron into apoferritin, the major iron storage protein of vertebrates, and that the ferroxidase activity of intestinal xanthine oxidase could be important in determining the fraction of iron within the intestinal mucosa cell partitioned to ferritin versus the iron that remains in a transient pool for rapid transport to plasma.
Biochem Mol Biol Int 1994 May
PMID:Xanthine oxidase: an efficient promoter of the iron loading of apoferritin. 795 Oct 57

Mammalian ferritins are 24-meric proteins composed of variable proportions of H and L-subunits. The L-chain, in contrast to the H-chain, lacks detectable ferroxidase activity, and its role in ferritin iron incorporation is unclear. In this study, apoferritins were subjected to iron loading with large iron increments to favour spontaneous iron hydrolysis. The homopolymers of the wild-type H-chain, and of a mutant H-chain with an inactivated ferroxidase centre, formed massive protein aggregates, while the L-chain homopolymers remained mostly soluble. The difference between H and L-ferritins was not related to the rate of iron oxidation or to the presence of preformed iron cores. Heteropolymers were constructed in vitro by co-renaturing different proportions of the H-chain with the L-chain or mutant H-chain with an inactivated ferroxidase centre. After loading with high iron increments, protein aggregation of the heteropolymers was reduced when the L-chain content was above 70 to 80%, either in combination with the wild-type H-chain or with the inactivated mutant H-chain. Under acidic conditions (pH 5.5, 1000 Fe atoms per molecule) the heteropolymers with about 20% H and 80% L-chains incorporated three to fourfold more iron into soluble 24-mers than the homopolymers. The data indicate that ferritins with more than 18 L-chains per molecule have the capacity to lower non-specific iron hydrolysis in bulk solution. This property is possibly due to a specific attraction of the incoming oxidized iron into the cavity and may be related to an effect of the L-chain on the cavity microenvironment. It is concluded that under high iron increments the ferritins with high L:H-chain ratios are the most efficient in incorporating iron, and this goes some way to explain why iron storage tissues contain L-rich isoferritins.
J Mol Biol 1994 May 20
PMID:The role of the L-chain in ferritin iron incorporation. Studies of homo and heteropolymers. 818 40

Disordered copper (Cu) metabolism in LEC rats, an animal model of Wilson disease, was characterized by specifying Cu in the liver, bloodstream and kidneys during the accumulation process and at the onset of jaundice; Cu accumulates in the liver with age in a form bound to metallothionein (MT). Massive Cu is liberated from MT when Cu accumulates beyond the capacity of MT synthesis. Cu bound to MT is not supplied to ceruloplasmin (Cp) during its maturation process, while the metal is transferred to Cu,zinc (Zn)-superoxide dismutase (SOD) directly from MT. Cu ions not bound to MT are transferred to Cp and the holo-Cp is excreted into the bloodstream near and at the onset of jaundice. Cu accumulated in the liver in a form bound to MT is removed selectively by tetrathiomolybdate (TTM), and the animal at the beginning of the onset of jaundice recovers by the chelation therapy. Mechanisms of the removal reaction were proposed to involve formation of MT/TTM, Cu/TTM, and/or polymeric Cu/TTM complexes according to the stoichiometry of TTM to Cu. The Cu/TTM complex was assumed to be effluxed into the bloodstream and to bind specifically to albumin. TTM is taken up by the liver in accordance with the Cu content. The toxicity of Cu was explained by the active oxygen species produced in Cu-mediated reactions, and the participation of MT.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Disordered copper metabolism in LEC rats, an animal model of Wilson disease: roles of metallothionein. 855 76

Ceruloplasmin (CP) is an important extracellular antioxidant and free radical scavenger. Although CP is expressed mainly in the liver, recent studies have identified the lung as another major site of CP synthesis. The sites and cell types that are responsible for CP expression in baboon and mouse lung are described. CP mRNA is detected in primordial bronchial epithelium in baboon fetuses by 60 days of gestation. At 140 days of gestation and thereafter, CP mRNA is found in airway epithelium and in the ductal cells of the submucosal glands. In developing and mature mice, CP mRNA is present in epithelial cells throughout the airway. In endotoxin-treated mice, the amount of CP mRNA increases several-fold in large airways but increases only moderately in small airways. This suggests that the high concentration of CP in the mucus lining of the upper airway, which serves to filter harmful substances, is particularly important during stressful conditions. Endotoxin treatment in mice also results in the induction of high levels of CP mRNA in a subset of alveolar wall cells. The data suggest that the airway epithelial cells are the major source of CP in the lung fluid and support ceruloplasmin's critical role in host defense against oxidative damage and infection in the lung.
Am J Respir Cell Mol Biol 1996 Feb
PMID:Cellular expression of ceruloplasmin in baboon and mouse lung during development and inflammation. 863 Feb 66

The effects of ceruloplasmin, a blu copper-containing serum glycoprotein, on the oxidation of the neurotoxin 6-hydroxydopamine in several chemical environments were studied. The spontaneous autoxidation of 6-hydroxydopamine proceeded by a free radical chain reaction involving O2-. and produced the corresponding chromogen 6-hydroxydopaminequinone and hydrogen peroxide. The process was accelerated in the presence of horse plasma ceruloplasmin. Yields of hydrogen peroxide in the presence of ceruloplasmin were significantly less than those measured in its absence. This is the first evidence of oxidase activity of ceruloplasmin toward a natural substrate, the 6-hydroxydopamine.
Biochem Mol Biol Int 1996 Apr
PMID:Effect of ceruloplasmin on 6-hydroxydopamine oxidation. 872 1

We report here on the characterization of a mutation in the ceruloplasmin gene in a 45 year old woman with insulin-dependent diabetes mellitus who presented with the recent onset of gait disturbance and dysarthria. Physical examination revealed an ataxic gait, scanning speech and retinal degeneration. Magnetic resonance imaging of the brain was consistent with increased basal ganglia iron content and laboratory studies revealed a low serum iron concentration and no detectable serum ceruloplasmin. Nucleotide sequence analysis of the ceruloplasmin gene from this patient revealed a G to A substitution in exon 15 resulting in a nonsense mutation at amino acid 858 (Trp858ter). The patient's younger, neurologically asymptomatic brother was also found to be homozygous for this mutation. Taken together the clinical and genetic data support the concept of an essential and unique role for ceruloplasmin in human iron metabolism. Identification of this kindred extends the spectrum of ceruloplasmin gene mutations resulting in this autosomal recessive, late-onset neurodegenerative disease and highlights the importance of recognizing aceruloplasminemia as a genetic cause of diabetes and neurologic disease.
Hum Mol Genet 1996 Jan
PMID:Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease. 878 43

The effect of curcumin on the biochemical changes induced by isoproterenol (ISO) administration in rats was examined. ISO (300 mg Kg-1 administered subcutaneously twice at an interval of 24 h) caused a decrease in body weight and an increase in heart weight, water content as well as in the levels of serum marker enzymes viz creatine kinase (CK), lactate dehydrogenase (LDH) and LDH1 isozyme. It also produced electrocardiographic changes such as increased heart rate, reduced R amplitude and ST elevation. Curcumin at a concentration of 200 mg.Kg-1, when administered orally, showed a decrease in serum enzyme levels and the electrocardiographic changes got restored towards normalcy. Myocardial infarction was accompanied by the disintegration of membrane polyunsaturated fatty acids expressed by increase of thiobarbituric acid reactive substance (TBARS), a measure of lipid peroxides and by the impairment of natural scavenging, characterized by the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, alpha tocopherol, reduced glutathione (GSH) and ascorbic acid. The oral pretreatment with curcumin two days before and during ISO administration decreased the effect of lipid peroxidation. It was shown to have a membrane stabilizing action by inhibiting the release of beta-glucuronidase from nuclei, mitochondria, lysosome and microsome. Curcumin pre- and co-treatment decreased the severity of pathological changes and thus, could have a protective effect against the damage caused by myocardial infarction (MI).
Mol Cell Biochem 1996 Jun 21
PMID:Protective role of curcumin against isoproterenol induced myocardial infarction in rats. 885 58

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism characterized by progressive neurodegeneration of the retina and basal ganglia in association with inherited mutations of the ceruloplasmin gene. To begin to elucidate the pathogenesis of this disease, ceruloplasmin gene expression was examined in human brain and retinal tissue. RNA blot analysis and RNAse protection studies demonstrate ceruloplasmin-specific transcripts in multiple regions of the human brain, and biosynthetic studies reveal ceruloplasmin synthesis and secretion in these same regions. Consistent with these observations, in situ hybridization of central nervous system tissue utilizing ceruloplasmin cRNA probes reveals abundant ceruloplasmin gene expression in specific populations of glial cells associated with the brain microvasculature, surrounding dopaminergic melanized neurons in the substantia nigra and within the inner nuclear layer of the retina. Taken in the context of the clinical and pathological features observed in patients with aceruloplasminemia, these data reveal that glial cell-specific ceruloplasmin gene expression is essential for iron homeostasis and neuronal survival in the human central nervous system.
Hum Mol Genet 1996 Dec
PMID:Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia. 896 53


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