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

We investigated the regulation and expression of ferritin in human cells by exposing peripheral blood monocytes (PBM) to heat shock (HS), opsonized sheep red blood cells (RBC), and iron. Iron induced ferritin but had no effect on stress protein expression. HS did not induce ferritin, indicating that ferritin is not a heat shock protein (HSP), at least in human PBM. In contrast, erythrophagocytosis (EP), a model for oxidative stress and endogenous iron release, induced HSP, heme oxygenase (HO), and ferritin. During EP, the antioxidant flavonoid quercetin prevented the induction of ferritin and HO, while it had no effect on the induction of ferritin by iron. In contrast, the iron chelator o-phenanthroline prevented the induction of ferritin during both EP and iron exposure. Differential effects of the transcriptional inhibitor actinomycin D on the various stress proteins revealed transcriptional regulation of HSP and HO during EP, whereas the induction of ferritin was posttranscriptionally regulated. We propose that while ferritin is not an HSP, its induction during EP is mediated through the action of ROS and is promoted by the iron released from RBC. Induction of ferritin and the subsequent iron sequestration may protect PBM from oxidative injury by limiting the iron-catalysed free radical reactions during EP.
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PMID:Differential regulation and expression of stress proteins and ferritin in human monocytes. 988 84

Sn protoporphyrin (SnPP) and Sn mesoporphyrin (SnMP), potent inhibitors of heme oxygenase (HO), significantly suppress bilirubin production, lower serum and biliary bilirubin levels and increase biliary heme output in animals and man. In this study, 20 healthy volunteers, 7 patients with primary biliary cirrhosis and 4 patients with idiopathic hemochromatosis were treated with SnPP and 4 healthy volunteers with SnMP. In all cases, serum ferritin levels increased substantially but transiently after administration of these HO inhibitors. Values returned to baseline within a few days. Infusion of hematin in 4 healthy volunteers did not significantly affect ferritin levels. No increases occurred in 7 other acute-phase reactants. The observation that these HO inhibitors transiently increase serum ferritin levels implies a link between ferritin, iron metabolism and HO activity which may be usefully explored in disorders of iron metabolism.
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PMID:Heme oxygenase inhibitors transiently increase serum ferritin concentrations without altering other acute-phase reactants in man. 1035 26

To examine whether increases in heme oxygenase (HO)-1 activity have protective effects on the oxidant-induced injury of airway epithelial cells, human tracheal epithelial cells were cultured on a porous filter membrane, and electrical conductance (G) and mannitol flux across epithelial membrane were measured with Ussing's chamber methods and D-[(3)H]mannitol, respectively. Hydrogen peroxide (H(2)O(2); 1 mM) increased G with time from the baseline value of 6.0 +/- 0.6 to 17.8 +/- 0.9 mS/cm(2) at 6 h after administration (P < 0.001). Likewise, H(2)O(2) significantly increased mannitol flux through the cultured epithelium (P < 0.01). Pretreatment of cultured epithelial cells with hemin (10 microM; 8 h) or interleukin (IL)-1beta (10 ng/ml; 16 h) completely inhibited increases in G and mannitol flux induced by H(2)O(2). Tin protoporphyrin IX (50 micrometer) and zinc protoporphyrin IX (10 microM), inhibitors of HO-1, reduced hemin-induced and IL-1beta-induced inhibitory effects. Hemin treatment increased HO-1 messenger RNA expression, HO-1 protein production, and HO activity and bilirubin content as well as ferritin content in the cultured epithelial cells. Pretreatment with hemin and desferoxamine, which, like ferritin, can bind iron, inhibited H(2)O(2)-induced increases in G and mannitol permeability. Although exogenous bilirubin mimicked hemin-induced inhibitory effects, exogenous apoferritin failed to inhibit H(2)O(2)-induced effects on G and mannitol permeability. These findings suggest that HO-1 induction provides protection against H(2)O(2)-induced injury of the cultured human airway epithelial cells in part via the HO-bilirubin pathway.
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PMID:Protective effects of heme oxygenase-1 against oxidant-induced injury in the cultured human tracheal epithelium. 1046 Jul 61

Interleukin 11 (IL-11) is a pleiotropic cytokine with biological activities on many different cell types. Recombinant human IL-11 (rhIL-11) is produced by recombinant DNA technology in Escherichia coli. Both in vitro and in vivo, rhIL-11 has shown effects on multiple hematopoietic cell types. Its predominant in vivo hematopoietic activity is the stimulation of peripheral platelet counts in both normal and myelosuppressed animals. This activity is mediated through effects on both early and late progenitor cells to stimulate megakaryocyte differentiation and maturation. rhIL-11 has been approved for the treatment of chemotherapy-induced thrombocytopenia. The hematopoietic effects of rhIL-11 are most likely direct effects on progenitor cells and megakaryocytes in combination with other cytokines or growth factors. rhIL-11 also induces secretion of acute phase proteins (ferritin, haptoglobin, C-reactive protein, and fibrinogen) from the liver. The induction of heme oxidase and inhibition of several P450 oxidases have been reported from in vitro studies. In vivo, rhIL-11 treatment decreases sodium excretion by the kidney by an unknown mechanism and induces hemodilution. rhIL-11 also exhibits anti-inflammatory effects in a variety of animal models of acute and chronic inflammation, including inflammatory bowel disease, inflammatory skin disease, autoimmune joint disease, and various infection-endotoxemia syndromes. rhIL-11 has trophic effects on non-transformed intestinal epithelium under conditions of mucosal damage. The mechanism of the anti-inflammatory activity of rhIL-11 has been extensively studied. rhIL-11 directly affects macrophage and T cell effector function. rhIL-11 inhibits tumor necrosis factor-alpha (TNF alpha), interleukin 1beta (IL-1beta), interleukin 12 (IL-12), interleukin 6 (IL-6), and nitric oxide (NO) production from activated macrophages in vitro. The inhibition of cytokine production was associated with inhibition of nuclear translocation of the transcription factor, nuclear factor kappa B (NF-kappaB). The block to NF-kappaB nuclear translocation correlates with the ability of rhIL-11 to maintain or enhance production of the inhibitors of NF-kappaB, IkappaB-alpha and IkappaB-beta. In addition to effects on macrophages, rhIL-11 also reduces CD4+ T cell production of Th1 cytokines, such as IFN gamma induced by IL-12, while enhancing Th2 cytokine production. rhIL-11 also blocks IFN gamma production in vivo. The molecular effects of rhIL-11 have also been studied in a clinical trial. Molecular analysis of skin biopsies of patients with psoriasis before and during rhIL-11 treatment demonstrates a decrease in mRNA levels of TNF alpha, IFN gamma and iNOS. These activities suggest that in addition to its thrombopoietic clinical use, rhIL-11 may also be valuable in the treatment of inflammatory diseases. The clinical utility of the anti-inflammatory properties of rhIL-11 is being investigated in patients with Crohn's disease, psoriasis and rheumatoid arthritis. These diseases are believed to be initiated and maintained by activated CD4+ Th1 cells in conjunction with activated macrophages.
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PMID:Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. 1048 79

Prostaglandins of the A type (PGA) exert a cytoprotective activity during hyperthermia and virus infection. This effect is associated with induction of heat shock proteins (HSP) in mammalian cells. We now report that, in human monocytes, PGA1 is able to induce the synthesis of the iron-binding, redox-regulated protein ferritin. L-chain ferritin induction is consequent to a substantial increase in the accumulation of L-chain ferritin transcripts in PGA1-treated cells, whereas H-chain ferritin is regulated post-transcriptionally, consequently to reduction of iron-regulatory protein binding to iron-responsive elements in ferritin mRNA. Ferritin induction is specific for cyclopentenone prostaglandins (PGA1, PGA2, PGJ2, Delta12-PGJ2), whereas other arachidonic acid (AA) metabolites have no effect. In human monocytes, PGA1 also induces heat shock gene transcription via heat shock factor activation, as well as the synthesis of the oxidative-stress protein heme oxygenase (HOS). Differently from HSP, the induction of ferritin by PGA1 is specific for monocytes. Monocytes/macrophages play a pivotal role in inflammation, controlling iron metabolism and releasing a variety of mediators, including proinflammatory reactive oxygen species (ROS), cytokines and AA metabolites. As ferritin, together with hsp70 and HO, plays a key role in protection from oxidant damage, these results suggest that PGA1 may have cytoprotective activity also during oxidative injury.
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PMID:Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation. 1049 Nov 19

The ultraviolet A (UVA, 320-400 nm) component of sunlight has the potential to generate an oxidative stress in cells and tissue so that antioxidants (both endogenous and exogenous) strongly influence the biological effects of UVA. The expression of several genes (including heme oxygenase-1, HO-1; collagenase; the CL100 phosphatase and the nuclear oncogenes, c-fos and c-jun) is induced following physiological doses of UVA to cells and this effect can be strongly enhanced by removing intracellular glutathione or enhancing singlet oxygen lifetime. We have observed that heme is released from microsomal heme-containing proteins by UVA and other oxidants and that activation of HO-1 expression by UVA correlates with levels of heme release. UVA radiation also leads to an increase in labile iron pools (either directly or via HO-1) and eventual increases in ferritin levels. The role of heme oxygenase in protection of skin fibroblasts is probably an emergency inducible defense pathway to remove heme liberated by oxidants. The slower increase in ferritin levels is an adaptive response which serves to keep labile iron pools low and thereby reduce Fenton chemistry and oxidant-induced chain reactions involving lipid peroxidation. In keratinocytes, the primary target of UVA radiation, heme oxygenase levels are constitutively high (because of HO-2 expression). Since there is a corresponding increase in basal levels of ferritin the epidermis appears to be well protected constitutively against the oxidative stress generated by UVA.
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PMID:Redox regulation and oxidant activation of heme oxygenase-1. 1051 38

The modification of ferritin in human skin cells in vitro and in vivo following infrared-A irradiation by immunohistochemical analysis and ELISA were evaluated. In addition, we observed that IR-A is not capable of inducing frank damage to DNA (pyrimidine dimers, p53), induction of oxidative stress proteins (heme oxygenase, nitric oxide, superoxide dismutase, heat shock proteins) or proteases (collagenase, stromelysin, gelatinase) involved in carcinogenesis and photoaging of the skin. in vivo, basal levels of ferritin were heterogeneous for all individuals tested but all showed ferritin to stain precisely in the basal layer of unirradiated epidermis. Following IR-A radiation, the ferritin increase was localized to epidermal tissue and showed an increase from 120 to 220%. Parallel to the in vivo analysis, dermal fibroblasts were cultured from six individuals. Quantitative analysis for ferritin in cultured fibroblasts was assessed by ELISA and increases were seen to be dose-dependent and up to 130% of basal levels of ferritin following infrared-A. Our findings indicate that the putative defense system of ferritin that exists in human skin in vivo can be induced by infrared-A radiation and that these wavelengths may prove to be beneficial for human skin. Importantly, following the same doses of IR-A that induced ferritin levels, there was no alteration seen for nuclear DNA type damage, oxidative stress proteins or proteases involved in the degradation of skin. The increased concentrations of this antioxidant in human skin following acute UV radiation could afford increased protection against subsequent oxidative stress.
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PMID:Induction of the putative protective protein ferritin by infrared radiation: implications in skin repair. 1067 64

Heme arginate infusions blunt the symptoms of patients with acute intermittent porphyria without evidence of the vascular or thrombotic side effects reported for hematin. To provide a rationale for heme arginate's safety, the present study examined the effects of various ferriporphyrins to sensitize human endothelial cells to free radical injury and to induce heme oxygenase and ferritin expression. Heme arginate, unlike hematin, did not amplify oxidant-induced cytotoxicity mediated by hydrogen peroxide (5.3 +/- 2.4 versus 62.3 +/- 5.3% (51)Cr release, P <.0001) or by activated neutrophils (14.4 +/- 2.9 versus 41.1 +/- 6.0%, P <.0001). Nevertheless, heme arginate efficiently entered endothelial cells similarly to hematin, since both markedly induced heme oxygenase mRNA (more than 20-fold increase) and enzyme activity. Even with efficient permeation, endothelial cell ferritin content was only minimally increased by heme arginate compared with a 10-fold induction by hematin; presumably less free iron was derived from heme arginate despite up-regulation of heme oxygenase. Hematin is potentially vasculopathic by its marked catalysis of oxidation of low-density lipoprotein (LDL) to endothelial-toxic moieties. Heme arginate was significantly less catalytic. Heme arginate-conditioned LDL was less than half as cytotoxic to endothelial cells as hematin-conditioned LDL (P <.004). It is concluded that heme arginate may be less vasculotoxic than hematin since it is an effective heme oxygenase gene regulator but a less efficient free-radical catalyst.
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PMID:Ferriporphyrins and endothelium: a 2-edged sword-promotion of oxidation and induction of cytoprotectants. 1082 27

Spontaneous intracerebral hemorrhage (ICH) is the stroke subtype with highest mortality and morbidity. ICH can also occur following traumatic brain injury and thrombolysis for ischemic stroke and myocardial infarction. Development of ICH-induced hemispheric edema can elevate intracranial pressure and cause death. In survivors, edema-related white matter injury can lead to life-long neurological deficits. At present, there are no scientifically proven treatments for ICH. Heme oxygenase products, particularly iron and bilirubin, can be toxic to cells. In cerebral ischemia models, metalloporphyrins that are potent heme oxygenase inhibitors, reduce edema and infarct size. Tin-mesoporphyrin (SnMP) is a neuroprotectant that has also been used clinically to treat hyperbilirubinemia. Presently, we tested the hypothesis that SnMP treatment would reduce edema development following experimental ICH. We produced hematomas in pentobarbital-anesthetized pigs (9-11 kg) by infusing autologous blood into the frontal white matter. To maximize tissue concentrations, SnMP (87.5 microM in DMSO) or DMSO (vehicle controls) was included in the infused blood. Pig brains were frozen in situ at 24 hrs. following ICH and hematoma and edema volumes were determined on coronal sections by computer-assisted image analysis. We also examined the effects of SnMP in vitro on ferritin iron release, the formation of iron-induced thiobarbituric acid reactive substances (TBARS) and initial clot formation and hemolysis. SnMP treatment significantly reduced intracerebral mass following ICH. This was due to significant decreases in hematoma (0.68+/-0.08 vs. 1.39+/-0.30 cc, vehicle controls p<0.025) and edema volumes (edema = 1. 16+/-0.33 vs. 1.77+/-0.31 cc, p<0.05). In vitro, SnMP did not stabilize ferritin iron against reductive release nor did it decrease iron-induced TBARS formation in brain homogenates. SnMP or DMSO added to pig blood did not alter clot weights. In conclusion, SnMP reduced intracerebral mass in an ICH model by decreasing both hematoma and edema volumes SnMP's mechanism of action is presently unknown but may involve its potent inhibition of heme oxygenase activity. SnMP's effect appears unrelated to ferritin iron release, antioxidant activity or initial clot formation. Since SnMP treatment could be brain protective following ICH, further investigations into neurological and neuropathological outcomes and as well as into its mechanism of action are warranted.
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PMID:Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. 1087 46

Hemoglobin is a key factor in the production of cerebral vasospasm. Metabolism of hemoglobin involves breakdown of heme by heme oxygenase (HO) and sequestration of the released iron in ferritin. We determined whether subarachnoid hemorrhage induces these proteins in cerebral arteries and, if so, in which cells they are produced. Whether the changes correlated with vasospasm also was investigated. Subarachnoid hemorrhage was created in monkeys, and vasospasm was assessed by angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage. Ferritin and HO-1 messenger ribonucleic acid (mRNA) and protein were measured by competitive reverse transcription-polymerase chain reaction and Western blotting in hemorrhage-side and control-side cerebral arteries and brain tissue. The location of these proteins was determined by immunohistochemistry. There was significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage. There were no significant changes in mRNA for HO-1 or ferritin in cerebral arteries or brain tissue at any time. There was a significant increase in HO-1 and ferritin protein in hemorrhage-side compared with control-side cerebral arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3 days, whereas the increase in ferritin protein was maximal at 7 days. There was no detectable increase in HO-1 or ferritin protein in brain tissue at any time. Immunohistochemistry localized HO-1 protein and ferritin to cells in the adventitia of the arterial wall. We show that subarachnoid hemorrhage is associated with a significant increase in HO-1 and ferritin proteins in cerebral arteries that begins at least as early as 3 days after the hemorrhage and that persists for up to 14 days.
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PMID:Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys. 1090 40


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