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Jonathan D. Gitlin - One of the best experts on this subject based on the ideXlab platform.
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a fungal multicopper oxidase restores iron homeostasis in aCeruloplasminemia
Blood, 2004Co-Authors: Leah Z Harris, Jonathan D. Gitlin, Sandra Daviskaplan, Jerry KaplanAbstract:Mutations that lead to a loss of the copper-containing plasma enzyme Ceruloplasmin disrupt mammalian iron homeostasis. The mechanism by which Ceruloplasmin mobilizes iron from cell stores has been controversial. We demonstrate that injection of a soluble copper-containing yeast protein Fet3p can restore iron homeostasis in phlebotomized mice with a deletion of the Ceruloplasmin gene. These results show the conservation of function of copper-containing proteins in eukaryotic iron metabolism.
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targeted gene disruption reveals an essential role for Ceruloplasmin in cellular iron efflux
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Leah Z Harris, Alison P Durley, Tszkwong Man, Jonathan D. GitlinAbstract:ACeruloplasminemia is an autosomal recessive disorder of iron metabolism. Affected individuals evidence iron accumulation in tissue parenchyma in association with absent serum Ceruloplasmin. Genetic studies of such patients reveal inherited mutations in the Ceruloplasmin gene. To elucidate the role of Ceruloplasmin in iron homeostasis, we created an animal model of aCeruloplasminemia by disrupting the murine Ceruloplasmin (Cp) gene. Although normal at birth, Cp−/− mice demonstrate progressive accumulation of iron such that by one year of age all animals have a prominent elevation in serum ferritin and a 3- to 6-fold increase in the iron content of the liver and spleen. Histological analysis of affected tissues in these mice shows abundant iron stores within reticuloendothelial cells and hepatocytes. Ferrokinetic studies in Cp+/+ and Cp−/− mice reveal equivalent rates of iron absorption and plasma iron turnover, suggesting that iron accumulation results from altered compartmentalization within the iron cycle. Consistent with this concept, Cp−/− mice showed no abnormalities in cellular iron uptake but a striking impairment in the movement of iron out of reticuloendothelial cells and hepatocytes. Our findings reveal an essential physiologic role for Ceruloplasmin in determining the rate of iron efflux from cells with mobilizable iron stores.
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aCeruloplasminemia molecular characterization of this disorder of iron metabolism
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Z L Harris, Y Takahashi, H Miyajima, M Serizawa, R T A Macgillivray, Jonathan D. GitlinAbstract:Abstract Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains 95% of the copper found in the plasma of vertebrate species. We report here on the identification of a genetic defect in the Ceruloplasmin gene in a patient previously noted to have a total absence of circulating serum Ceruloplasmin in association with late-onset retinal and basal ganglia degeneration. In this patient T2 (transverse relaxation time)-weighted magnetic resonance imaging of the brain revealed basal ganglia densities consistent with iron deposition, and liver biopsy confirmed the presence of excess iron. Although Southern blot analysis of the patient's DNA was normal, PCR amplification of 18 of the 19 exons composing the human Ceruloplasmin gene revealed a distinct size difference in exon 7. DNA sequence analysis of this exon revealed a 5-bp insertion at amino acid 410, resulting in a frame-shift mutation and a truncated open reading frame. The validity of this mutation was confirmed by analysis of DNA from the patient's daughter, which revealed heterozygosity for this same 5-bp insertion. The presence of this mutation in conjunction with the clinical and pathologic findings demonstrates an essential role for Ceruloplasmin in human biology and identifies aCeruloplasminemia as an autosomal recessive disorder of iron metabolism. These findings support previous studies that identified Ceruloplasmin as a ferroxidase and are remarkably consistent with recent studies on the essential role of a homologous copper oxidase in iron metabolism in yeast. The clinical and laboratory findings suggest that additional patients with movement disorders and nonclassical Wilson disease should be examined for Ceruloplasmin gene mutations.
Leah Z Harris - One of the best experts on this subject based on the ideXlab platform.
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a fungal multicopper oxidase restores iron homeostasis in aCeruloplasminemia
Blood, 2004Co-Authors: Leah Z Harris, Jonathan D. Gitlin, Sandra Daviskaplan, Jerry KaplanAbstract:Mutations that lead to a loss of the copper-containing plasma enzyme Ceruloplasmin disrupt mammalian iron homeostasis. The mechanism by which Ceruloplasmin mobilizes iron from cell stores has been controversial. We demonstrate that injection of a soluble copper-containing yeast protein Fet3p can restore iron homeostasis in phlebotomized mice with a deletion of the Ceruloplasmin gene. These results show the conservation of function of copper-containing proteins in eukaryotic iron metabolism.
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copper transport and metabolism are normal in aCeruloplasminemic mice
Journal of Biological Chemistry, 2001Co-Authors: Laura A Meyer, Alison P Durley, Joseph R Prohaska, Leah Z HarrisAbstract:Abstract Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of the copper found in the plasma of vertebrate species. Although this protein is known to function as an essential ferroxidase, the role of Ceruloplasmin in copper transport and metabolism remains unclear. To elucidate the role of Ceruloplasmin in copper metabolism, the kinetics of copper absorption, transport, distribution, and excretion were examined utilizing64Cu in wild-type and aCeruloplasminemic mice. No differences in gastrointestinal absorption, hepatic uptake, or biliary excretion were observed in these animals. Furthermore, steady state measurements of tissue copper content utilizing 64Cu and atomic absorption spectroscopy revealed no differences in the copper content of the brain, heart, spleen, and kidney. Consistent with these findings, the activity of copper-zinc superoxide dismutase in these tissues was equivalent in wild-type and Ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in aCeruloplasminemic mice because of the loss of ferroxidase function. Hepatic copper content was markedly increased in aCeruloplasminemic mice. As no differences were observed in copper absorption or biliary copper excretion, these data suggest that in these animals, hepatocyte copper intended for Ceruloplasmin incorporation is trafficked into a compartment that is less available for biliary copper excretion. Taken together, these data reveal no essential role for Ceruloplasmin in copper metabolism and suggest a previously unappreciated complexity to the subcellular distribution of this metal within the hepatocyte secretory pathway.
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targeted gene disruption reveals an essential role for Ceruloplasmin in cellular iron efflux
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Leah Z Harris, Alison P Durley, Tszkwong Man, Jonathan D. GitlinAbstract:ACeruloplasminemia is an autosomal recessive disorder of iron metabolism. Affected individuals evidence iron accumulation in tissue parenchyma in association with absent serum Ceruloplasmin. Genetic studies of such patients reveal inherited mutations in the Ceruloplasmin gene. To elucidate the role of Ceruloplasmin in iron homeostasis, we created an animal model of aCeruloplasminemia by disrupting the murine Ceruloplasmin (Cp) gene. Although normal at birth, Cp−/− mice demonstrate progressive accumulation of iron such that by one year of age all animals have a prominent elevation in serum ferritin and a 3- to 6-fold increase in the iron content of the liver and spleen. Histological analysis of affected tissues in these mice shows abundant iron stores within reticuloendothelial cells and hepatocytes. Ferrokinetic studies in Cp+/+ and Cp−/− mice reveal equivalent rates of iron absorption and plasma iron turnover, suggesting that iron accumulation results from altered compartmentalization within the iron cycle. Consistent with this concept, Cp−/− mice showed no abnormalities in cellular iron uptake but a striking impairment in the movement of iron out of reticuloendothelial cells and hepatocytes. Our findings reveal an essential physiologic role for Ceruloplasmin in determining the rate of iron efflux from cells with mobilizable iron stores.
Samuel David - One of the best experts on this subject based on the ideXlab platform.
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Ceruloplasmin replacement therapy ameliorates neurological symptoms in a preclinical model of aCeruloplasminemia
EMBO molecular medicine, 2017Co-Authors: Alan Zanardi, Samuel David, Alberto Piperno, Antonio Conti, Marco Cremonesi, Patrizia D'adamo, Enrica Gilberti, Pietro Apostoli, Carlo Vittorio Cannistraci, Massimo AlessioAbstract:Abstract ACeruloplasminemia is a monogenic disease caused by mutations in the Ceruloplasmin gene that result in loss of protein ferroxidase activity. Ceruloplasmin plays a role in iron homeostasis, and its activity impairment leads to iron accumulation in liver, pancreas, and brain. Iron deposition promotes diabetes, retinal degeneration, and progressive neurodegeneration. Current therapies mainly based on iron chelation, partially control systemic iron deposition but are ineffective on neurodegeneration. We investigated the potential of Ceruloplasmin replacement therapy in reducing the neurological pathology in the Ceruloplasmin‐knockout (CpKO) mouse model of aCeruloplasminemia. CpKO mice were intraperitoneal administered for 2 months with human Ceruloplasmin that was able to enter the brain inducing replacement of the protein levels and rescue of ferroxidase activity. Ceruloplasmin‐treated mice showed amelioration of motor incoordination that was associated with diminished loss of Purkinje neurons and reduced brain iron deposition, in particular in the choroid plexus. Computational analysis showed that Ceruloplasmin‐treated CpKO mice share a similar pattern with wild‐type animals, highlighting the efficacy of the therapy. These data suggest that enzyme replacement therapy may be a promising strategy for the treatment of aCeruloplasminemia.
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involvement of glycosylphosphatidylinositol linked Ceruloplasmin in the copper zinc nitric oxide dependent degradation of glypican 1 heparan sulfate in rat c6 glioma cells
Journal of Biological Chemistry, 2004Co-Authors: Fang Cheng, Birgitta Havsmark, Samuel DavidAbstract:The core protein of glypican-1, a glycosylphosphatidylinositol-linked heparan sulfate proteoglycan, can bind Cu(II) or Zn(II) ions and undergo S-nitrosylation in the presence of nitric oxide. Cu(II)-to-Cu(I)-reduction supports extensive and permanent nitrosothiol formation, whereas Zn(II) ions appear to support a more limited, possibly transient one. Ascorbate induces release of nitric oxide, which catalyzes deaminative degradation of the heparan sulfate chains on the same core protein. Although free Zn(II) ions support a more limited degradation, Cu(II) ions support a more extensive self-pruning process. Here, we have investigated processing of glypican-1 in rat C6 glioma cells and the possible participation of the copper-containing glycosylphosphatidylinositol-linked splice variant of Ceruloplasmin in nitrosothiol formation. Confocal microscopy demonstrated colocalization of glypican-1 and Ceruloplasmin in endosomal compartments. Ascorbate induced extensive, Zn(II)-supported heparan sulfate degradation, which could be demonstrated using a specific zinc probe. RNA interference silencing of Ceruloplasmin expression reduced the extent of Zn(II)-supported degradation. In cell-free experiments, the presence of free Zn(II) ions prevented free Cu(II) ion from binding to glypican-1 and precluded extensive heparan sulfate autodegradation. However, in the presence of Cu(II)-loaded Ceruloplasmin, heparan sulfate in Zn(II)-loaded glypican-1 underwent extensive, ascorbate-induced degradation. We propose that the Cu(II)-to-Cu(I)-reduction that is required for S-nitrosylation of glypican-1 can take place on Ceruloplasmin and thereby ensure extensive glypican-1 processing in the presence of free Zn(II) ions.
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expression of a membrane bound form of the ferroxidase Ceruloplasmin by leptomeningeal cells
Glia, 2003Co-Authors: Bina Mittal, Bharatkumar N Patel, Mohammad M Doroudchi, Suh Young Jeong, Samuel DavidAbstract:Ceruloplasmin is a key enzyme involved in detoxifying ferrous iron, which can generate free radicals. The secreted form of Ceruloplasmin is produced by the liver and is abundant in serum. We have previously identified a membrane-bound glycosylphosphatidylinositol (GPI)-anchored form of Ceruloplasmin (GPI-Cp) that is expressed by astrocytes in the central nervous system (CNS) (Patel and David. 1997. J Biol Chem 272:20185-20190). We now provide direct evidence that rat leptomeningeal cells, which cover the surface of the brain, also express GPI-Cp. The expression of GPI-Cp on the surface of these cells increases with postnatal development and is regulated in vitro by cell density, time in culture, and various extracellular matrix molecules. The expression of GPI-Cp also appears to be regulated differently in astrocytes and leptomeningeal cells in vitro. The abundant expression of GPI-Cp on the surface of leptomeningeal cells suggests that these cells play a role in antioxidant defense along the surface of the postnatal CNS possibly by detoxifying the cerebrospinal fluid.
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alternative rna splicing generates a glycosylphosphatidylinositol anchored form of Ceruloplasmin in mammalian brain
Journal of Biological Chemistry, 2000Co-Authors: Bharatkumar N Patel, Robert J. Dunn, Samuel DavidAbstract:Abstract Ceruloplasmin is a copper-containing ferroxidase that is essential for normal iron homeostasis. Whereas Ceruloplasmin in plasma is produced and secreted by hepatocytes, in the brain a glycosylphosphatidylinositol (GPI)-anchored form of Ceruloplasmin is expressed on the surface of astrocytes. By using a cDNA cloning approach, we have now determined that the GPI-anchored form of Ceruloplasmin is generated by alternative RNA splicing. The splicing occurs downstream of exon 18 and replaces the C-terminal 5 amino acids of the secreted form with an alternative 30 amino acids that signal GPI anchor addition. RNase protection analysis demonstrates that the GPI-anchored form is the major form in the brain, whereas the secreted form predominates in the liver. Individuals with aCeruloplasminemia, a hereditary deficiency of Ceruloplasmin, have severe iron deposition in a number of organs, including the brain where it results in neurodegeneration. Therefore, this novel GPI-anchored form of Ceruloplasmin is likely to play an important role in iron metabolism in the central nervous system.
Hiroaki Miyajima - One of the best experts on this subject based on the ideXlab platform.
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ACeruloplasminemia with Abnormal Compound Heterozygous Mutations Developed Neurological Dysfunction during Phlebotomy Therapy.
Internal medicine (Tokyo Japan), 2018Co-Authors: Maki Watanabe, Ken Ohyama, Masashi Suzuki, Yasunobu Nosaki, Takashi Hara, Katsushige Iwai, Satoshi Kono, Hiroaki Miyajima, Kenji MokunoAbstract:ACeruloplasminemia is an autosomal recessive inherited disorder caused by Ceruloplasmin gene mutations. The loss of ferroxidase activity of Ceruloplasmin due to gene mutations causes a disturbance in cellular iron transport. We herein describe a patient with aCeruloplasminemia, who presented with diabetes mellitus that was treated by insulin injections, liver hemosiderosis treated by phlebotomy therapy, and neurological impairment. A genetic analysis of the Ceruloplasmin gene revealed novel compound heterozygous mutations of c.1286_1290insTATAC in exon 7 and c.2185delC in exon 12. This abnormal compound heterozygote had typical clinical features similar to those observed in aCeruloplasminemia patients with other gene mutations.
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chapter 45 aCeruloplasminemia
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition), 2015Co-Authors: Satoshi Kono, Hiroaki MiyajimaAbstract:ACeruloplasminemia is an autosomal recessive disorder of iron homeostasis that is classified as an inherited neurodegenerative disorder called “neurodegeneration with brain iron accumulation” (NBIA). This disorder is caused by loss-of-function mutations encoding the Ceruloplasmin gene. The clinical presentation involves hepatic iron overload, microscopic anemia, retinal degeneration, diabetes mellitus, and neurological symptoms, including cerebellar ataxia, involuntary movements and cognitive dysfunction. The diagnosis of aCeruloplasminemia is made based on the complete absence of serum Ceruloplasmin, marked elevation of the ferritin concentration and abnormally low levels of intensity in the liver and brain, including the basal ganglia, thalamus, and dentate nucleus, on both T1- and T2-weighted magnetic resonance imaging (MRI). Pathological and molecular biological investigations have revealed the pathogenesis of neurodegeneration to involve iron-mediated radical cellular injury resulting from marked accumulation of iron in the affected parenchymal tissues due to an iron efflux impairment caused by the absence of ferroxidase activity of Ceruloplasmin.
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Biological effects of mutant Ceruloplasmin on hepcidin-mediated internalization of ferroportin
Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010Co-Authors: Satoshi Kono, Tatsuhiro Terada, Naohisa Tomosugi, Kenichi Yoshida, Yasushi Hamaya, Shigeru Kanaoka, Hiroaki MiyajimaAbstract:Ceruloplasmin plays an essential role in cellular iron efflux by oxidizing ferrous iron exported from ferroportin. Ferroportin is posttranslationally regulated through internalization triggered by hepcidin binding. ACeruloplasminemia is an autosomal recessive disorder of iron homeostasis resulting from mutations in the Ceruloplasmin gene. The present study investigated the biological effects of glycosylphosphatidylinositol (GPI)-linked Ceruloplasmin on the hepcidin-mediated internalization of ferroportin. The prevention of hepcidin-mediated ferroportin internalization was observed in the glioma cells lines expressing endogenous Ceruloplasmin as well as in the cells transfected with GPI-linked Ceruloplasmin under low levels of hepcidin. A decrease in the extracellular ferrous iron by an iron chelator and incubation with purified Ceruloplasmin in the culture medium prevented hepcidin-mediated ferroportin internalization, while the reconstitution of apo-Ceruloplasmin was not able to prevent ferroportin internalization. The effect of Ceruloplasmin on the ferroportin stability was impaired due to three distinct properties of the mutant Ceruloplasmin: namely, a decreased ferroxidase activity, the mislocalization in the endoplasmic reticulum, and the failure of copper incorporation into apo-Ceruloplasmin. Patients with aCeruloplasminemia exhibited low serum hepcidin levels and a decreased ferroportin protein expression in the liver. The findings supported the notion that under low levels of hepcidin, mutant Ceruloplasmin cannot stabilize ferroportin because of a loss-of-function in the ferroxidase activity, which has been reported to play an important role in the stability of ferroportin. The properties of mutant Ceruloplasmin regarding the regulation of ferroportin may therefore provide a therapeutic strategy for aCeruloplasminemia patients.
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treatment of symptomatic heterozygous aCeruloplasminemia with oral zinc sulphate
Brain & Development, 2007Co-Authors: Jens Kuhn, Hiroaki Miyajima, Yoshitomo Takahashi, H Bewermeyer, K F Kuhn, T U HoogenraadAbstract:ACeruloplasminemia is an autosomal recessive and phenotypically primarily neurodegenerative disease caused by a homozygous mutation of the Ceruloplasmin gene. The absence of Ceruloplasmin and its ferroxidase activity leads to pathological iron overload in the brain and other organs. While heterozygous carriers of Ceruloplasmin gene mutations have been believed to be asymptomatic, a number of cases with neurological deficits have recently been described. To date, an effective treatment has not been established for either aCeruloplasminemia or symptomatic heterozygous aCeruloplasminemia. The present report concerns the beneficial treatment of an 18-year-old girl with extrapyramidal and cerebellar-mediated movement disorder caused by a heterozygous mutation of the Ceruloplasmin gene using oral zinc sulphate.
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Identification and in silico characterization of a novel compound heterozygosity associated with hereditary aCeruloplasminemia.
Scandinavian journal of gastroenterology, 2007Co-Authors: Wolf Peter Hofmann, Hiroaki Miyajima, Yoshitomo Takahashi, Christoph Welsch, Ulrike Mihm, Christoph Krick, Stefan Zeuzem, Christoph SarrazinAbstract:Background. Hereditary aCeruloplasminemia is an adult-onset autosomal recessive disease characterized by increased iron overload in the liver, pancreas, retina, and central nervous system. So far, 45 families with cases of aCeruloplasminemia have been reported world-wide and mainly missense and nonsense mutations in the Ceruloplasmin gene were detected. Material and methods. Here, we report the identification, clinical characterization, and in silico analysis of a novel compound heterozygosity in the Ceruloplasmin gene of a 31-year-old man with iron overload. Results. Increased serum ferritin levels, elevated iron saturation, as well as results of iron quantification in the liver and magnetic resonance imaging-based measurement of T2 relaxation times of the substantia nigra consistently suggested iron overload. By sequencing the Ceruloplasmin gene, so far unknown nucleotide replacements G229C, and C2131A were detected in exons 2 and 12, respectively. In silico analyses showed that the resulting amino acid...
Herken H - One of the best experts on this subject based on the ideXlab platform.
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disorder: a case control study
2019Co-Authors: Virit O, Selek S, Bulut M, Erel O, Ha Savas, Celik H, Herken HAbstract:Background: Alterations in Ceruloplasmin are currently assumed as one of the mechanisms underlying the development of a number of neurodegenerative disorders. Several studies indicate that elevated serum Ceruloplasmin levels may play a role in schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. No study investigating the relationship between Ceruloplasmin and obsessive-compulsive disorder (OCD) has been published to date. Nowadays OCD is increasingly speculated to be a different disorder than other anxiety disorders, and rather is considered to be more similar to psychotic disorders. The objective of this study to explore whether there is an association of Ceruloplasmin with OCD as in schizophrenia.Method: 26 pure OCD and 9 co-morbid OCD patients from Gaziantep University Sahinbey Research Hospital, Psychiatry Clinics, diagnosed according to the DSM IV and 40 healthy controls were included in the study. Blood samples were collected; Ceruloplasmin levels were measured.Results: The mean Ceruloplasmin level in pure OCD patients, co-morbid OCD patients, and control group persons were 544.46 +/- 26.53, 424.43 +/- 31.50 and 222.35 +/- 8.88 U/L respectively. Results of all 3 groups differ significantly. Positive predictive value of Ceruloplasmin for that cut-off point is 31/31 (100%) and negative predictive value is 40/44 (91%) in our group.Conclusion: Although the nature of relationship is not clear there was an association between Ceruloplasmin levels and OCD in our study
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Level in Patients with First-Episode Depression: A Longitidunal Study
'Elsevier BV', 2012Co-Authors: Mc Kaya, Selek S, Bulut M, Ha Savas, Bez Y, If Karababa, Celik H, Herken HAbstract:Background and Aims. Ceruloplasmin, an acute phase reactant with antioxidant capacity, has been found to be increased in some psychiatric disorders like schizophrenia and obsessive compulsive disorder. However, studies in depression are very scarce. We under-took this study determine the serum Ceruloplasmin levels of depressive patients before and after treatment, to compare them with those of healthy control subjects, and to assess any possible association of Ceruloplasmin and treatment response.Methods. Nineteen (8 male, 11 female) patients with major depressive disorder and 40 (17 male, 23 female) healthy control subjects were included in the study. The patients received naturalistic antidepressant treatment for 8 weeks after diagnosis. Serum Ceruloplasmin levels and Hamilton Depression Rating Scale (HAM-D) scores of the patients were measured before and after their antidepressant treatment. Blood collection for Ceruloplasmin measurement was done only once for healthy control subjects.Results. Patients' Ceruloplasmin levels before and after antidepressant treatment were significantly higher than control subjects (t = 7.569, p < 0.001 and t = 6.764, p < 0.001, respectively). Despite clinical improvement, Ceruloplasmin did not show any significant change after treatment in patients with depression (t = -1.163, p = 0.260) and remained higher than levels of control subjects. No correlation was found between HAM-D score, presence of response, and Ceruloplasmin levels.Conclusions. Compared to healthy control subjects, Ceruloplasmin level seemed to be higher in patients with depression and remained high, despite acute antidepressant treatment. Improvement in clinical measurements of depression after antidepressant treatment was not reflected as significant alterations in serum Ceruloplasmin levels. (C) 2012 IMSS. Published by Elsevier Inc
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Increased Plasma Ceruloplasmin Levels in Schizophrenia
KURE ILETISIM GRUBU A S, 2008Co-Authors: Virit O, Altindag A, Selek S, Yumru M, Bulut M, Erel O, Ha Savas, Herken HAbstract:Objective: Ceruloplasmin is a protein in the human serum that is synthesized by hepatocytes, but extrahepatic gene expression in the brain, lung, spleen, and testis has also been reported. Ceruloplasmin contains approximately 95% of serum copper and it carries copper from liver to numerous tissues. Ceruloplasmin level reflects largely the copper concentration of the serum. However, Ceruloplasmin has also an antioxidant function that is known as the acute phase reactant. Additionally, Ceruloplasmin has a role in the oxidation of serotonin, epinephrine, and norepinephrine. Abnormalities in Ceruloplasmin levels have been associated with several neurodegenerative diseases. Moreover, the alteration of plasma Ceruloplasmin levels has been linked to schizophrenia and its some clinical characteristics including acute or chronic phase, the length of the disease or whether the patients on treatment or not. However, there exists a controversy on relationship between the plasma level of Ceruloplasmin and schizophrenia. There are number of reports on the increased or decreased and/or normal level of plasma Ceruloplasmin in association with schizophrenia, These differences may have been originated from the usage of different measurement methods, clinical situations, and ethnobiological differences. In the present study, we aimed to investigate the association between plasma Ceruloplasmin level and schizophrenic in Turkish patients.Methods: 60 patients (36 women and 24 men, mean of age 31.93 +/- 9.37 years, range 19-55) that were diagnosed as schizophrenia according to DSM-IV were induced for this study at the Psychotic Disorders Unit, Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. The control group consisted of 40 healthy subjects in similar age and gender (23 women, 17 men). Venous blood samples were collected from the left forearm into heparinized tubes The blood samples were centrifuged and the plasma was removed, Erel's Ceruloplasmin measurement method that is based on the enzymatic oxidation of ferrous ions to ferric ions was used. SPSS Windows program 13.0 was applied for statistical analysis.Results: Plasma Ceruloplasmin levels of schizophrenic patients were significantly higher than the healthy controls (p < 0.001), In addition, female patients had higher Ceruloplasmin levels than male patients (p < 0.001), while there was no statistically significant difference between women and men in the control group. There was no association between the Ceruloplasmin levels and the age, the duration of illness, smoking, schizophrenia subtypes, symptom severity, and antipsychotic therapy.Conclusions: The study suggests that Ceruloplasmin may play a role in pathophysiology of schizophrenic, Moreover, female patients having a higher level of Ceruloplasmin than those of male patients that is first time reported in the literature. However, further studies are needed to clarify the higher level of Ceruloplasmin in schizophrenia and to reveal the importance of the gender differences in Ceruloplasmin levels in schizophrenia
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Increased plasma Ceruloplasmin levels in schizophrenia
2008Co-Authors: Virit O, Altindag A, Selek S, Yumru M, Bulut M, Erel O, Savas H.a., Herken HAbstract:Objective: Ceruloplasmin is a protein in the human serum that is synthesized by hepatocytes, but extrahepatic gene expression in the brain, lung, spleen, and testis has also been reported. Ceruloplasmin contains approximately 95% of serum copper and it carries copper from liver to numerous tissues. Ceruloplasmin level reflects largely the copper concentration of the serum. However, Ceruloplasmin has also an antioxidant function that is known as the acute phase reactant. Additionally, Ceruloplasmin has a role in the oxidation of serotonin, epinephrine, and norepinephrine. Abnormalities in Ceruloplasmin levels have been associated with several neurodegenerative diseases. Moreover, the alteration of plasma Ceruloplasmin levels has been linked to schizophrenia and its some clinical characteristics including acute or chronic phase, the length of the disease or whether the patients on treatment or not. However, there exists a controversy on relationship between the plasma level of Ceruloplasmin and schizophrenia. There are number of reports on the increased or decreased and/or normal level of plasma Ceruloplasmin in association with schizophrenia. These differences may have been originated from the usage of different measurement methods, clinical situations, and ethnobiological differences. In the present study, we aimed to investigate the association between plasma Ceruloplasmin level and schizophrenia in Turkish patients. Methods: 60 patients (36 women and 24 men, mean of age 31.93±9.37 years, range 19-55) that were diagnosed as schizophrenia according to DSM-IV were included for this study at the Psychotic Disorders Unit, Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. The control group consisted of 40 healthy subjects in similar age and gender (23 women, 17 men). Venous blood samples were collected from the left forearm into heparinized tubes. The blood samples were centrifuged and the plasma was removed. Erel's Ceruloplasmin measurement method that is based on the enzymatic oxidation of ferrous ions to ferric ions was used. SPSS Windows program 13.0 was applied for statistical analysis. Results: Plasma Ceruloplasmin levels of schizophrenic patients were significantly higher than the healthy controls (p