Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6-hydroxydopamine (6-OHDA) proved to be a very effective agent for iron release from ferritin. Iron release was enhanced in the presence of SOD, catalase and under anaerobic conditions. Ascorbic acid, a well known agent able to release iron from ferritin, increased the amount of released iron in more than an additive manner when used in combination with 6-OHDA. Similar to 6-OHDA, 6-hydroxydopa (Topa) and 1,2,4-benzenetriol were also able to release iron in large amounts; in contrast, catecholamines and other benzenediols were comparatively ineffective.
 ...
PMID:Release of iron from ferritin by 6-hydroxydopamine under aerobic and anaerobic conditions. 212 9

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
 ...
PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

The Escherichia coli Fur protein, with its iron(II) cofactor, represses iron assimilation and manganese superoxide dismutase (MnSOD) genes, thus coupling iron metabolism to protection against oxygen toxicity. Iron assimilation is triggered by iron starvation in wild-type cells and is constitutive in fur mutants. We show that iron metabolism deregulation in fur mutants produces an iron overload, leading to oxidative stress and DNA damage including lethal and mutagenic lesions. fur recA mutants were not viable under aerobic conditions and died after a shift from anaerobiosis to aerobiosis. Reduction of the intracellular iron concentration by an iron chelator (ferrozine), by inhibition of ferric iron transport (tonB mutants), or by overexpression of the iron storage ferritin H-like (FTN) protein eliminated oxygen sensitivity. Hydroxyl radical scavengers dimethyl sulfoxide and thiourea also provided protection. Functional recombinational repair was necessary for protection, but SOS induction was not involved. Oxygen-dependent spontaneous mutagenesis was significantly increased in fur mutants. Similarly, SOD deficiency rendered sodA sodB recA mutants nonviable under aerobic conditions. Lethality was suppressed by tonB mutations but not by iron chelation or overexpression of FTN. Thus, superoxide-mediated iron reduction was responsible for oxygen sensitivity. Furthermore, overexpression of SOD partially protected fur recA mutants. We propose that a transient iron overload, which could potentially generate oxidative stress, occurs in wild-type cells on return to normal growth conditions following iron starvation, with the coupling between iron and MnSOD regulation helping the cells cope.
 ...
PMID:Lethal oxidative damage and mutagenesis are generated by iron in delta fur mutants of Escherichia coli: protective role of superoxide dismutase. 773 Feb 58

The in vivo production of HO- requires iron ions, H2O2 and O2- or other oxidants but probably does not occur through the Haber-Weiss reaction. Instead oxidants, such as O2-, increase free iron by releasing Fe(II) from the iron-sulfur clusters of dehydratases and by interfering with the iron-sulfur clusters reassembly. Fe(II) then reduces H2O2, and in turn Fe(III) and the oxidized cluster are re-reduced by cellular reductants such as NADPH and glutathione. In this way, SOD cooperates with cellular reductants in keeping the iron-sulfur clusters intact and the rate of HO. production to a minimum. O2- and other oxidants can release iron from Fe(II)-containing enzymes as well as copper from thionein. The released Fe(III) and Cu(II) are then reduced to Fe(II) and Cu(I) and can then participate in the Fenton reaction. In mammalian cells oxidants are able to convert cytosolic aconitase into active IRE-BP, which increases the "free" iron concentration intracellularly both by decreasing the biosynthesis of ferritin and increasing biosynthesis of transferrin receptors. The biological role of the soxRS regulon of Escherichia coli, which is involved in the adaptation toward oxidative stress, is presumably to counteract the oxidative inactivation of the iron clusters and the subsequent release of iron with consequent increased rate of production of HO.
 ...
PMID:The role of iron-sulfur clusters in in vivo hydroxyl radical production. 890 35

Redox-active forms of iron are known to catalyze free radical mediated peroxidative reactions. There is scanty information on such effects at the sites of iron absorption. This was tested in iron-deficient WKY female rats supplemented for 15 days with FeSO4 equivalent to 8 mg of iron (D+) and compared with iron deficient (D) and iron adequate (C) rats. The levels of intestinal MDA and protein carbonyls and the activities of various antioxidant enzymes were estimated. As markers of functional integrity, the activities of alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were evaluated. In addition, we measured the concentrations of ferritin, transferrin, and ceruloplasmin levels in serum and in intestinal mucosa. It was observed that correction of iron deficiency resulted in significant increase in MDA and protein carbonyl formation. Activities of both alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were significantly decreased in D+ compared to C. The increase in catalase and decrease in Gpx was found to be sensitive to iron administration. Neither iron deficiency nor its correction had any effect on the activity of SOD and GSH levels. Iron supplementation has resulted in decreased mobilization of stored iron as reflected by increased mucosal ferritin level and decreased serum ceruloplasmin ferroxidase activity contributing to greater peroxidative stress in the intestine. These results suggest that iron-deficient intestine of rat is more susceptible to iron-mediated peroxidative damage and functional impairment during correction of deficiency with iron.
 ...
PMID:Iron-deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. 980 Oct 65

We investigated dopamine (DA)- and DOPA-related release of iron from ferritin, and lipid peroxidation of liposomes induced by the released iron. Iron release increased with increasing DA or DOPA concentrations. Effects of SOD and an oxygen-reduced environment indicated that superoxide was partly responsible for iron release. The released iron induced lipid peroxidation at relatively low concentrations of DA or DOPA, while at high concentrations, peroxidation was inhibited. These findings indicate that the risk of lipid peroxidation depends on the DA/iron or DOPA/iron ratio even if the iron concentration is low. Our findings suggest that DA-containing neurons are always at risk of oxidative damage. Furthermore, DOPA therapy may modify the nigral degeneration by reducing or accelerating ferritin iron-dependent lipid peroxidation.
 ...
PMID:Dopamine and DOPA cause release of iron from ferritin and lipid peroxidation of liposomes. 1050 26

Gout affects mostly males over 40 years old and, occasionally, postmenopausal women. This pattern coincides with the pattern of iron accumulation. On the other hand, menstruating women are seldom afflicted by gout, because the monthly blood loss causes them to accumulate iron to a much lesser degree. Gout involves seven aspects: (1) uric acid overproduction from increased purines in the diet; (2) uric acid overproduction from ATP degradation; (3) uric acid overproduction from increased de novo synthesis of purines; (4) uric acid overproduction from increased DNA breakdown from cell damage; (5) decreased uric acid elimination, caused by molybdenum and sulfur binding to copper in the kidneys; (6) precipitation of sodium urate-iron crystals in the joints due to high ferritin and saturated transferrin and low CuZn-SOD and Cu-thionein in the joint; (7) development of inflammation, triggered by tyrosine bonding to the sodium-urate-iron crystals and being transformed by tyrosine kinase. Alcohol and iron greatly affect most of these aspects. Therefore, phlebotomy is suggested as therapy for gout patients, in order to eliminate the accumulated Fe. Furthermore, yearly blood donation is recommended for males with a family history of gout, so as to prevent Fe accumulation and avoid gout.
 ...
PMID:Effect of gradual accumulation of iron, molybdenum and sulfur, slow depletion of zinc and copper, ethanol or fructose ingestion and phlebotomy in gout. 1061 42

The antioxidant defense system in liver tissue in experimental hyperthyroidism and/or in iron supplementation was investigated. Thyroid hormones (T3, T4, TSH), ferritin (marker of iron status), antioxidant status components (glutathione [GSH], glutathione peroxidase [GSH-Px], superoxide dismutase [SOD]), and serum transaminases (GOT and GPT, both of which are known to be released from damaged hepatocytes), were measured. Hyperthyroidism in rats, induced by L-thyroxine administration, significantly raised SOD activity (p < 0.05), but significantly decreased GSH-Px activity and GSH values (p < 0.001) in the liver. In the L-thyroxine administered and iron supplemented (TI) group, GSH and GSH-Px values of liver tissues were significantly lower than those of control rats (p < 0.05). GSH-Px levels of the TI group were higher (p < 0.001), and SOD levels significantly lower (p < 0.001) than those of the L-thyroxine administered group. We conclude that hyperthyroidism induces SOD activity in liver; ferritin levels increase in hyperthyroidism, contributing to the antioxidant defense system; GSH-Px and GSH levels are decreased significantly in hyperthyroidism either due to inactivation due to increased oxidative stress or to insufficient synthesis; iron supple- and GPT analysis); iron decreases the effect of T4. This must be taken into consideration during iron supplementation.
 ...
PMID:Evaluation of antioxidant status in liver tissues: effect of iron supplementation in experimental hyperthyroidism. 1063 95

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.
 ...
PMID:Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia. 1140 60

Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis.
 ...
PMID:Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord. 1176 70


1 2 3 4 5 Next >>