Glial Fibrillary Acidic Protein is Greatly Modified by Oxidative Stress in Aceruloplasminemia Brain

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin (Cp) gene. The neuropathological hallmark of this disease is intracellular iron overload, which is thought to lead to neuronal cell death through increased oxidative stress. We evaluated...

Full description

Saved in:
Bibliographic Details
Published inFree radical research Vol. 36; no. 3; pp. 303 - 306
Main Authors Kaneko, Kazuma, Nakamura, Akihiro, Yoshida, Kunihiro, Kametani, Fuyuki, Higuchi, Keiichi, Ikeda, Shu-ichi
Format Journal Article
LanguageEnglish
Published England Informa UK Ltd 01.03.2002
Taylor & Francis
Subjects
Aceruloplasminemia
Astrocyte
Brain - metabolism
Brain - pathology
Brain Diseases - etiology
Brain Diseases - metabolism
Ceruloplasmin - deficiency
Electrophoresis, Gel, Two-Dimensional
Female
Glial Fibrillary Acidic Protein
Glial Fibrillary Acidic Protein - metabolism
Humans
Lipid Peroxidation
Malondialdehyde
Middle Aged
Mutation
Neurons - metabolism
Neurons - pathology
Oxidative Stress
Peptide Fragments - analysis
Protein Carbonyl
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Online AccessGet full text

Cover

More Information
Summary:Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin (Cp) gene. The neuropathological hallmark of this disease is intracellular iron overload, which is thought to lead to neuronal cell death through increased oxidative stress. We evaluated and characterized protein oxidation in the brain of a patient with this disease. The protein carbonyl content in the cerebral cortex of the patient was elevated compared to controls. Furthermore, peptide mass fingerprinting and partial amino acid sequencing identified glial fibrillary acidic protein (GFAP) as the major carbonylated protein in the cerebral cortex of the patient. In conjunction with the facts that Cp mainly localizes to astrocytes in the central nervous system and that astrocytes are loaded with much more iron than neurons in the cerebral cortex, our findings indicate that Cp deficiency may primarily damage astrocytes. We speculate that the dysfunction of astrocytes may be causatively related to neuronal cell loss in aceruloplasminemia.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1071-5762
1029-2470
DOI:10.1080/10715760290019327