Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention

Handle URI:
http://hdl.handle.net/10754/555663
Title:
Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention
Authors:
Olivieri, S.; Conti, A.; Iannaccone, S.; Cannistraci, C. V.; Campanella, A.; Barbariga, M.; Codazzi, F.; Pelizzoni, I.; Magnani, G.; Pesca, M.; Franciotta, D.; Cappa, S. F.; Alessio, M.
Abstract:
Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson's disease patients. Parkinson's disease ceruloplasmin profiles proved more acidic than those found in healthy controls and in other human neurological diseases (peripheral neuropathies, amyotrophic lateral sclerosis, and Alzheimer's disease); degrees of acidity correlated with patients' pathological grading. Applying an unsupervised pattern recognition procedure to the two-dimensional electrophoresis images, we identified representative pathological clusters. In vitro oxidation of CSF in two-dimensional electrophoresis generated a ceruloplasmin shift resembling that observed in Parkinson's disease and co-occurred with an increase in protein carbonylation. Likewise, increased protein carbonylation was observed in Parkinson's disease CSF, and the same modification was directly identified in these samples on ceruloplasmin. These results indicate that ceruloplasmin oxidation contributes to pattern modification in Parkinson's disease. From the functional point of view, ceruloplasmin oxidation caused a decrease in ferroxidase activity, which in turn promotes intracellular iron retention in neuronal cell lines as well as in primary neurons, which are more sensitive to iron accumulation. Accordingly, the presence of oxidized ceruloplasmin in Parkinson's disease CSF might be used as a marker for oxidative damage and might provide new insights into the underlying pathological mechanisms.
KAUST Department:
Integrative Systems Biology Lab; Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention 2011, 31 (50):18568 Journal of Neuroscience
Publisher:
Society for Neuroscience
Journal:
Journal of Neuroscience
Issue Date:
14-Dec-2011
DOI:
10.1523/JNEUROSCI.3768-11.2011
Type:
Article
ISSN:
0270-6474; 1529-2401
Additional Links:
http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.3768-11.2011
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division; Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorOlivieri, S.en
dc.contributor.authorConti, A.en
dc.contributor.authorIannaccone, S.en
dc.contributor.authorCannistraci, C. V.en
dc.contributor.authorCampanella, A.en
dc.contributor.authorBarbariga, M.en
dc.contributor.authorCodazzi, F.en
dc.contributor.authorPelizzoni, I.en
dc.contributor.authorMagnani, G.en
dc.contributor.authorPesca, M.en
dc.contributor.authorFranciotta, D.en
dc.contributor.authorCappa, S. F.en
dc.contributor.authorAlessio, M.en
dc.date.accessioned2015-05-25T08:22:02Zen
dc.date.available2015-05-25T08:22:02Zen
dc.date.issued2011-12-14en
dc.identifier.citationCeruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention 2011, 31 (50):18568 Journal of Neuroscienceen
dc.identifier.issn0270-6474en
dc.identifier.issn1529-2401en
dc.identifier.doi10.1523/JNEUROSCI.3768-11.2011en
dc.identifier.urihttp://hdl.handle.net/10754/555663en
dc.description.abstractParkinson's disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson's disease patients. Parkinson's disease ceruloplasmin profiles proved more acidic than those found in healthy controls and in other human neurological diseases (peripheral neuropathies, amyotrophic lateral sclerosis, and Alzheimer's disease); degrees of acidity correlated with patients' pathological grading. Applying an unsupervised pattern recognition procedure to the two-dimensional electrophoresis images, we identified representative pathological clusters. In vitro oxidation of CSF in two-dimensional electrophoresis generated a ceruloplasmin shift resembling that observed in Parkinson's disease and co-occurred with an increase in protein carbonylation. Likewise, increased protein carbonylation was observed in Parkinson's disease CSF, and the same modification was directly identified in these samples on ceruloplasmin. These results indicate that ceruloplasmin oxidation contributes to pattern modification in Parkinson's disease. From the functional point of view, ceruloplasmin oxidation caused a decrease in ferroxidase activity, which in turn promotes intracellular iron retention in neuronal cell lines as well as in primary neurons, which are more sensitive to iron accumulation. Accordingly, the presence of oxidized ceruloplasmin in Parkinson's disease CSF might be used as a marker for oxidative damage and might provide new insights into the underlying pathological mechanisms.en
dc.publisherSociety for Neuroscienceen
dc.relation.urlhttp://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.3768-11.2011en
dc.rightsArchived with thanks to Journal of Neuroscienceen
dc.titleCeruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retentionen
dc.typeArticleen
dc.contributor.departmentIntegrative Systems Biology Laben
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalJournal of Neuroscienceen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionProteome Biochemistryen
dc.contributor.institutionClinical Neurosciencesen
dc.contributor.institutionItalian Institute of Technology Network–Molecular Neuroscienceen
dc.contributor.institutionCellular Neurophysiologyen
dc.contributor.institutionExperimental Neurology Institute, San Raffaele Scientific Institute, I-20132 Milan, Italyen
dc.contributor.institutionLaboratory of Neuroimmunology, Istituto di Ricovero e Cura a Carattere Scientifico, National Neurological Institute Mondino, I-27100 Pavia, Italyen
kaust.authorCannistraci, Carloen
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