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)

Partially-reduced forms of dioxygen or "oxy-radicals" (superoxide, O2-/HO2; hydrogen peroxide, H2O2; hydroxyl radical X OH) and oxidants of comparable reactivity are implicated in an increasing number of physiological, toxicological, and pathological states. Transition metal catalysis is recognized as being integral to the generation and the reactions of these activated oxygen species. Factors such as pH and chelation govern the reactivity of the transition metals with dioxygen and "oxy-radicals" and therefore influence the apparent mechanisms by which oxidative damage to phospholipids, DNA, and other biomolecules is initiated. In biological systems the concentrations of redox-active transition metals capable of catalyzing these reactions appears to be relatively low. However, under certain conditions metal storage and transport proteins (ferritin, transferrin, ceruloplasmin, etc.) may furnish additional redox active metals.
 ...
PMID:Role of metals in oxygen radical reactions. 301 69

We showed previously that treatment of cultured rabbit lens epithelial cells (LECs) with hyperbaric oxygen (HBO) produced DNA strand-breaks, caused reversible inhibition of protein synthesis and induced the synthesis of a 32 kD protein. In the present work, we employed immunostaining procedures to identify the 32 kD protein as heme oxygenase-1 (HO-1). Increased synthesis of the enzyme was observed as early as 12 hr after HBO-treatment, reached a maximum at 18 hr and was not detectable at 36 hr. Exposure of the cells to hemin also increased the synthesis of HO-1. An HBO-induced inhibition of protein synthesis and the subsequent induction of HO-1 was also observed in the capsule-epithelium of cultured rabbit lenses. For both LECs and the cultured lens, only HO-1 and not heme oxygenase-2 was HBO-inducible. Use of the antioxidant dimethylthiourea with HBO-treated lenses or LECs did not alter the observed effects on protein synthesis or the induction of HO-1. In contrast to results obtained with 50 atm O2, a pressure of 25 atm O2 inhibited protein synthesis only slightly and failed to induce synthesis of the 32 kD protein (although, as shown previously, identical exposure of LECs to 25 atm O2 significantly damaged DNA). Inhibition of protein synthesis in LECs and cultured lenses with the use of puromycin also induced synthesis of HO-1. Both hemin (10 micron), a source of iron, and 50 atm O2 produced a three-fold increase in the concentration of ferritin, a natural iron chelator, in LECs two days after exposure; no effects on ferritin levels were observed after 1 or 3 days. The finding that the increase in ferritin concentration occurred in the cells significantly after hemin- or HBO-induced synthesis of heme oxygenase indicates that chelatable iron rather than the heme molecule itself may have been the primary agent responsible for inducing ferritin synthesis. The data suggest that HBO-induced synthesis of HO-1 in the lens epithelium may be the result of an inhibition of protein synthesis, possibly leading to an accumulation of heme, rather than a direct protective response against oxidative stress.
 ...
PMID:Heme oxygenase synthesis is induced in cultured lens epithelium by hyperbaric oxygen or puromycin. 929 80

Hereditary hemochromatosis is characterized by marked variation of expression of the defect: very few homozygotes with the C282Y/C282Y HFE genotype have full-blown clinical disease, a larger number show biochemical stigmata of iron overload, and some seem normal biochemically. The following candidate genes have been examined in detail to determine whether polymorphisms in them may be responsible for this variation: transferrin, transferrin receptor 1, transferrin receptor 2, ferritin-L, ferritin-H, IRP1, IRP2, HFE, beta(2) microglobulin, mobilferrin/calreticulin, ceruloplasmin, ferroportin, NRAMP1, NRAMP2 (DMT1), haptoglobin, heme oxygenase-1, heme oxygenase-2, hepcidin, USF2, ZIRTL, duodenal cytochrome b ferric reductase (DCYTB), TNFalpha, keratin 8, and keratin 18. The coding sequence, exon-intron junctions, and promoters of each of these genes was sequenced in DNA from 20 subjects: 5 HFE C282Y/C282Y with clinical disease, 5 HFE C282Y/C282Y with normal/low ferritin levels and no disease, 5 wt/wt with high ferritin and transferrin saturation, and 5 wt/wt normal controls. When coding or promoter polymorphisms were encountered, DNA from large numbers of ethnically defined subjects was examined for these polymorphisms and a relationship between their existence and abnormalities of iron homeostasis was sought. Only in the case of one transferrin mutation did we find a strong relationship between the polymorphism and iron deficiency anemia. The putative genes that affect the expression of HFE mutations remain elusive.
 ...
PMID:Seeking candidate mutations that affect iron homeostasis. 1254 38

The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to establish a cell model of Alzheimer's disease. Graded concentration and time course experiments demonstrate that curcumin significantly upregulates phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor E2-related factor-2 (Nrf2), heme oxygenase 1 and ferritin expression, and that it significantly downregulates heme oxygenase 2, reactive oxygen species and amyloid-beta 40/42 expression. These effects of curcumin on PI3K, Akt and Nrf2 were blocked by LY294002 (PI3k inhibitor) and NF-E2-related factor-2 siRNA. The results indicate that the cytoprotection conferred by curcumin on APPswe transfected SH-SY5Y cells is mediated by its ability to regulate the balance between heme oxygenase 1 and 2 via the PI3K/Akt/Nrf2 intracellular signaling pathway.
...
PMID:Protective effects of curcumin in APPswe transfected SH-SY5Y cells. 2577 81