Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The expression of heme oxygenase-1 (HO-1) is increased in the CNS of mice and rats with experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). To investigate the role of HO-1 in EAE, a putative inhibitor [tin-protoporphyrin IX (Sn-PP IX)] of HO-1 was administered to SJL mice during active disease. Sn-PP IX (200 micromol/kg) attenuated clinical scores, weight loss, and some signs of pathology in comparison to vehicle treatment. Glutathione levels were greater in treated EAE mice than in those receiving vehicle, indicating lower oxidative stress in the former group. These data suggest that inhibition of HO-1 attenuated disease and suppressed free radical production. In the SJL model of EAE, extravasated blood is present in the CNS, and iron released by HO-1 from this heme source may not be adequately sequestered by ferritin, allowing for iron-mediated tissue damage. Thus, HO-1 may act to amplify the disease process in this model.
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PMID:Heme oxygenase-1 in SJL mice with experimental allergic encephalomyelitis. 1292 42

Multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune disorders resulting in demyelination in the central nervous system (CNS). Pathologically, the blood-brain barrier becomes damaged, macrophages and T cells enter into the CNS, oligodendrocytes and myelin are destroyed, astrocytes and microglia undergo gliosis, and axons become transected. Data from several biochemical and pharmacological studies indicate that free radicals participate in the pathogenesis of EAE, and iron has been implicated as the catalyst leading to their formation. The primary focus of this article is the examination of the role of iron in the pathogenesis of MS and EAE. Particular attention will be paid to the role and distribution of iron and proteins involved with iron metabolism (e.g., transferrin, ferritin, heme oxygenase-1, etc.) in normal and disease states of myelin. Furthermore, therapeutic interventions aimed at iron, iron-binding proteins, and substrates or products of iron-catalyzed reactions leading to free radical production will be discussed.
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PMID:The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis. 1510 71

This study evaluates levels of cerebrospinal fluid (CSF) brain-specific proteins (BSP) in subjects with optic neuritis (ON) who are at high risk of progression to multiple sclerosis (MS). Forty-one subjects had acute ON and 17 subjects with other neurological diseases (OND) served as controls. Twenty-one subjects with ON had white matter lesions on magnetic resonance imaging (MRI) and intrathecal synthesis of oligoclonal IgG bands (OB) consistent with being at high risk of progression to MS; eight of whom later were diagnosed with clinically definite MS (CDMS). Levels of S100B, ferritin and two neurofilament heavy chain phosphoforms (NfH(SM134) and NfH(SM135)) were analysed using ELISA technique. A putative index of 'axonal health' was expressed as a ratio of NfH(SM134) to NfH(S135). NfH(SM134) and the NfH(SM134:SM135) were significantly elevated in subjects with ON compared to controls. No significant differences in levels of CSF BSP were seen between ON subjects with CDMS plus those at high risk of progression to MS and ON subjects with normal MRI and negative CSF analysis. In conclusion, there is evidence of axonal damage in subjects who present with ON, which is independent of the diagnosis of CDMS.
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PMID:Cerebrospinal fluid levels of brain specific proteins in optic neuritis. 1522 88

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.
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PMID:Imaging iron stores in the brain using magnetic resonance imaging. 1573 84

Over the last few years, increased evidence has supported the role of iron dysregulation in the pathogenesis of multiple sclerosis (MS), as iron is essential for myelin formation and oxidative phosphorylation. We studied indices of iron metabolism, such as serum iron, ferritin, transferrin and soluble transferrin receptor (sTFR) levels in 27 MS patients. Seven patients had chronic progressive active disease (CP-A), six had chronic progressive stable (CP-S), ten had relapsing remitting active (RR-A) and four had relapsing-remitting stable (RR-S) disease. sTFR levels were found to be significantly higher in CP-A (P = 0.021) and RR-A (P < 0.004) patients than in controls. sTFR levels were also elevated in CP-S patients but did not reach significance (P = 0.064). sTFR values in RR-S patients were comparable to those found in controls (P = 0.31). Ferritin levels were significantly elevated only in CP-A patients (P < 0.002). Patients of the CP group had significantly higher ferritin values than the RR patients (P < 0.004). Haemoglobin values as well as iron and transferrin levels were within normal limits in all patients. In conclusion, the increased serum sTFR and ferritin levels in nonanaemic MS patients with active disease reflect the increased iron turnover. The mild elevation of sTFR levels in CP-S patients may indicate active inflammation with ongoing oxidative damage that is not detectable by history or examination.
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PMID:Serum ferritin, transferrin and soluble transferrin receptor levels in multiple sclerosis patients. 1595 6

Caucasian South African patients with multiple sclerosis (MS) were screened for the most common hereditary haemochromatosis (HH) mutations, H63D and C282Y, in order to determine the impact of iron overload on clinical outcome of MS. DNA screening for mutations H63D and C282Y in 118 apparently unrelated MS patients did not reveal significant differences in allele frequencies in comparison with a control group from the same population. Of 17 MS patients heterozygous for C282Y, 3 had below normal and none had above normal transferrin saturation levels. One of the index MS patients, and subsequently also her sister who also has MS, tested positive for two copies of mutation C282Y. Determination of iron status revealed high serum ferritin and transferrin saturation levels in both patients. However, the index patient, being unaware of her C282Y status, had received treatment for iron deficiency in the past and her MS symptoms were less severe than those of her sister who has been wheelchair bound for the past 12 years and who did not take iron supplements. Lack of clinical manifestation of HH without any signs of organ damage in the C282Y homozygous MS patients is in accordance with a role of iron dysregulation in the aetiology of MS.
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PMID:Lack of clinical manifestation of hereditary haemochromatosis in South African patients with multiple sclerosis. 1685 Feb 57

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.
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PMID:Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. 1778 27

This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfH(SM135)--a biomarker of axonal damage--in relation to nitric oxide (NO) metabolites: nitrate and nitrite (NOx) during acute multiple sclerosis (MS) relapse. Thirty-four relapsing-remitting MS (RR-MS) patients during acute relapse and 12 controls were enrolled. Patients were assessed on Expanded Disability Status Scale (EDSS) and underwent lumbar puncture within two weeks following relapse. Twenty patients were available for further follow-up and were assessed on EDSS 6-8 weeks since the relapse onset. The CSF NOx (P<0.0001), NfH(SM135) (P=0.01) and S100B (P=0.009) but not ferritin (P>0.05) were significantly raised in MS group. There was a significant correlation between CSF ferritin and S100B in RR-MS group (P=0.004). CSF NOx did not correlate with S100B and ferritin in study groups. RR-MS patients with detectable NfH(SM135) levels had higher NOx compared with subjects having undetectable NfH(SM135) (P=0.03). In the follow-up study, raised baseline levels of NOx (P=0.016) or NfH(SM135) (P=0.04) inversely correlated with the clinical recovery grade expressed as relative EDSS change between baseline and follow-up. In conclusion, NO metabolites were increased and because of their correlation with a biomarker of axonal degeneration (neurofilaments) and a measure for clinical disability (EDSS), relapse-related nitrosative stress is likely to be relevant to the development of sustained disability in an individual patient.
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PMID:Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis. 1789 12

Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1alpha) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.
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PMID:Hyperferritinemia in autoimmunity. 1830 May 83

Serum ferritin levels have been found to be increased in patients with active progressive multiple sclerosis (MS). However, its levels are reported to be unchanged in stable and in active relapsing-remitting (RR) form of the disease. No research to date has assessed the influence of interferon beta (IFN-beta) on ferritin concentrations. In this study, serum ferritin levels were measured in 43 individuals with RR-MS and 38 age- and sex-matched control volunteers. There were no significant differences between controls and patients under stable and untreated conditions. In patients at 12 months after the beginning of IFN-beta therapy, ferritin levels were higher in women and in men, in comparison with baseline (71.4 +/- 58.6 vs 43.4 +/- 29.9 ng/mL, P = 0.0006 and 216.0 +/- 124.3 vs 127.8 +/- 74.9 ng/mL, P = 0.0022, respectively). These results suggest that larger prospective studies are required to evaluate the role of serum ferritin in MS and its potential usefulness in monitoring responses to immunomodulatory therapies.
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PMID:Interferon beta therapy increases serum ferritin levels in patients with relapsing-remitting multiple sclerosis. 1857 25


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