Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P02794 (
ferritin
)
17,525
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ferritin levels were measured in postmortem brain tissue from patients dying with Parkinson's disease [treated with
L-3,4-dihydroxyphenylalanine
(
L-DOPA
)] and from control patients. Ferritin levels were decreased in the substantia nigra, caudate-putamen, globus pallidus, cerebral cortex, and cerebellum when compared with age-matched control tissues. However, in CSF from
L-DOPA
-treated patients and in serum from
L-DOPA
-treated and untreated parkinsonian patients,
ferritin
levels were normal. Previous studies have suggested an increased total iron content in substantia nigra of parkinsonian brain. The failure of substantia nigra
ferritin
formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease. The reason for decreased
ferritin
levels throughout the parkinsonian brain is not clear but does not seem to reflect a general system deficit in
ferritin
.
...
PMID:Decreased ferritin levels in brain in Parkinson's disease. 235 17
As neuroblastoma, the most common solid tumour in childhood, may contain all the constituents of the catecholamine biosynthesis cascade, some of these constituents may be produced in excess in a varying mixture reflecting the wide variability in expression of differentiated features of the tumour. We have measured plasma levels of norepinephrine (NE), epinephrine (E), dopamine (DA) and
3,4-dihydroxyphenylalanine
(DOPA), and plasma activities of dopamine beta-hydroxylase (DBH) and aromatic L-amino acid decarboxylase (ALAAD) in 18 patients with neuroblastoma, in 13 at various times during the course of their disease. Activities of serum lactic dehydrogenase (LDH), serum levels of
ferritin
(
FER
) and neuron-specific enolase (NSE), and urinary vanilmandelic acid (VMA) were also determined. NE, E and DBH were found not to reflect tumour activity. In untreated active neuroblastoma DOPA or ALAAD (10 out of 10) or both (six out of 10) were clearly elevated. In all 13 patients where samples were obtained during chemotherapy, ALAAD activities fell within the normal range, while DOPA decreased more slowly. During relapse, DOPA and, especially, ALAAD, rapidly increased; in all six patients who had a relapse both DOPA and ALAAD were elevated. In complete remission (eight patients), ALAAD was normal in all patients, but DOPA remained elevated in the one patient who later experienced a relapse. Our preliminary conclusion is that combined measurements of plasma ALAAD and DOPA may be useful markers for neuroblastoma activity at diagnosis, but even more so in indicating residual disease (DOPA) and in the early detection of relapse (ALAAD).
...
PMID:Combined measurements of plasma aromatic L-amino acid decarboxylase and DOPA as tumour markers in diagnosis and follow-up of neuroblastoma. 250 83
The restless legs syndrome (RLS) is one of the most common and unpleasant complaints of uremic patients. The pathophysiology of the RLS is still unclear. Various factors, including anemia and iron deficiency, are proposed to play a major role. We determined the prevalence of RLS in all stable hemodialysis patients under long-term treatment in two dialysis centers (n = 136) and compared the clinical and biochemical findings of patients with RLS and without RLS. Twenty-three percent of all patients investigated fulfilled the diagnostic criteria of RLS according to the International Restless Legs Syndrome Study Group. There were no statistical differences between the two groups regarding age, duration of uremia and need for dialysis, time on dialysis per week, hemoglobin, hematocrit, erythrocytes, s-
ferritin
, s-transferrin, s-iron, calcium, and standard biochemical indices, except for intact parathyroid hormone (iPTH) levels. Uremic patients with RLS showed significantly lower iPTH (P < 0.01) concentrations. In addition, the RLS group received a significantly higher number and dosage of psychopharmacological drugs, (ie,
L-DOPA
), than patients without RLS. These biochemical findings suggest that neither the severity of anemia nor that of iron deficiency has to be considered a major pathophysiological factor in established RLS. The significantly lower iPTH secretion in uremic patients with RLS, however, is a new finding, and further investigations will be necessary to determine whether this result is of any clinical significance to this group of patients. The significantly higher number of psychopharmacological drugs prescribed to uremic patients with RLS may be related to the symptoms of RLS.
...
PMID:Clinical and biochemical findings in uremic patients with and without restless legs syndrome. 946 5
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
Mn(III)-loaded
apoferritin
is promptly reduced to Mn(II)-
apoferritin
by the oxidation of
L-DOPA
to melanin. The process is nicely witnessed by a marked relaxation enhancement of water proton relaxation rate that has been detected both in cultured melanoma cells and in tumor animal models.
...
PMID:Mn loaded apoferritin as an MRI sensor of melanin formation in melanoma cells. 2227
Iron homeostasis is essential for the integrity of brain monoaminergic functions and its deregulation might be involved in neurological movement disorders such as the restless legs syndrome (RLS). Although iron metabolism breakdown concomitantly appears with monoaminergic system dysfunction in iron-deficient rodents and in RLS patients, the direct consequences of peripheral iron deficiency in the central nervous system (CNS) of non-human primates have received little attention. Here, we evaluated the peripheral iron-depletion impact on brain monoamine levels in macaque monkeys. After documenting circadian variations of iron and iron-related proteins (hemoglobin,
ferritin
and transferrin) in both serum and cerebrospinal fluid (CSF) of normal macaques, repeated blood withdrawals (RBW) were used to reduce peripheral iron-related parameter levels. Decreased serum iron levels were paradoxically associated with increased CSF iron concentrations. Despite limited consequences on tissue monoamine contents (dopamine - DA, 3, 4-dihydroxyphenylacetic acid - DOPAC, homovanillic acid, L-3, 4-dihydroxyphenylalanine -
L-DOPA
, 5-8 hydroxytryptamine - 5-HT, 5-hydroxyindoleacetic acid - 5-HIAA and noradrenaline) measured with post-mortem chromatography, we found distinct and region-dependent relationships of these tissue concentrations with CSF iron and/or serum iron and/or blood hemoglobin. Additionally, striatal extracellular DA, DOPAC and 5-HIAA levels evaluated by in vivo microdialysis showed a substantial increase, suggesting an overall increase in both DA and 5-HT tones. Finally, a trending increase in general locomotor activity, measured by actimetry, was observed in the most serum iron-depleted macaques. Taken together, our data are compatible with an increase in nigrostriatal DAergic function in the event of iron deficiency and point to a specific alteration of the 5-HT/DA interaction in the CNS that is possibly involved in the etiology of RLS.
...
PMID:Blood withdrawal affects iron store dynamics in primates with consequences on monoaminergic system function. 2566 8
Ferritin is a giant protein composed of 24 subunits which is able to sequester up to 4500 atoms of iron. We proposed two kinds of heme binding sites in mammalian ferritins and provided direct evidence for peroxidase activity of heme-
ferritin
, since there is the possibility that "ferritin-heme" systems display unexpected catalytic behavior like heme-containing enzymes. In the current study, peroxidase activity of heme-bound
ferritin
was studied using TMB(1), l-
DOPA
, serotonin, and dopamine, in the presence of H2O2, as oxidant substrate. The catalytic oxidation of TMB was consistent with first-order kinetics with respect to
ferritin
concentration. Perturbation of the binding affinity and catalytic behavior of heme-bound His-modified
ferritin
were also documented. We also discuss the importance of the peroxidase-/nitrative-mediated oxidation of vital molecules as well as
ferritin
-induced catalase inhibition using in vitro experimental system. Uncontrollable "heme-ferritin"-based enzyme activity as well as up-regulation of heme and
ferritin
may inspire that some oxidative stress-mediated cytotoxic effects in AD-affected cells could be correlated to
ferritin
-heme interaction and/or
ferritin
-induced catalase inhibition and describe its contribution as an important causative pathogenesis mechanism in some neurodegenerative disorders.
...
PMID:Heme-coordinated histidine residues form non-specific functional "ferritin-heme" peroxidase system: Possible and partial mechanistic relevance to oxidative stress-mediated pathology in neurodegenerative diseases. 2721 14