Glial fibrillary acidic protein is a major target of glycoxidative and lipoxidative damage in Pick's disease

• Published in: Journal of neurochemistry 2006-10, Vol.99 (1), p.177-185
• Main Authors: Muntané, G., Dalfó, E., Martínez, A., Rey, M. J., Avila, J., Pérez, M., Portero, M., Pamplona, R., Ayala, V., Ferrer, I.
• Format: Article
• Language: English
• Subjects: Aldehydes - pharmacology; Autopsy; Biochemistry; Biological and medical sciences; Brain - pathology; Chemical and industrial products toxicology. Toxic occupational diseases; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Glycosylation; glycoxidation; Humans; hydroxy‐2‐nonenal; Lipids; lipoxidation; Magnetic Resonance Imaging; Mass Spectrometry; Medical sciences; Metals and various inorganic compounds; Nerve Tissue Proteins - metabolism; Neurological disorders; Neurology; Neurons; Oxidation; Oxidative Stress; Pick Disease of the Brain - metabolism; Pick's disease; Proteins; Reference Values; Tomography, X-Ray Computed; Toxicology
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04032.x

Pick's disease is a subset of fronto‐temporal dementia characterised by severe atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied by astrocytic gliosis enriched in glial acidic protein. The remaining neurones have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick bodies, in addition to hyperphosphorylated tau in astrocytes and oligodendrocytes. Gel electrophoresis and western blotting using markers of glycoxidation (advanced glycation end products, N‐carboxyethyl‐lysine and N‐carboxymethyl‐lysine: AGE, CEL, CML, respectively) and lipoxidation (4‐hydroxy‐2‐nonenal: HNE, and malondialdehyde‐lysine: MDAL) were used in the frontal and occipital cortex in three Pick's disease cases and three age‐matched controls. In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands. Bi‐dimensional gel electrophoresis and western blotting also disclosed increased amounts and numbers of glial acidic protein isoforms in the frontal cortex in Pick's disease. Moreover, redox proteomics showed glycoxidation, as revealed with anti‐CEL antibodies and lipoxidation using anti‐HNE antibodies, of at least three glial acidic protein isoforms. The present results demonstrate that glial acidic protein is a target of oxidative damage in the frontal cortex in Pick's disease.