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 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.
Kaneko
Kazuma
K
Third Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Nakamura
Akihiro
A
Yoshida
Kunihiro
K
Kametani
Fuyuki
F
Higuchi
Keiichi
K
Ikeda
Shu-ichi
S
D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism*; D002570:Ceruloplasmin / Q000172:deficiency*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde; D008875:Middle Aged; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D008315:Malondialdehyde; D002570:Ceruloplasmin