Oxidation of Cytosolic Proteins and Expression of Creatine Kinase BB in Frontal Lobe in Different Neurodegenerative Disorders

• Published in: Dementia and geriatric cognitive disorders Vol. 10; no. 2; pp. 158 - 165
• Main Authors: Aksenova, M.V., Aksenov, M.Y., Payne, R.M., Trojanowski, J.Q., Schmidt, M.L., Carney, J.M., Butterfield, D.A., Markesbery, W.R.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.03.1999; S. Karger AG
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - enzymology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Biological and medical sciences; Blotting, Western; Creatine Kinase - biosynthesis; Cytosol - enzymology; Cytosol - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electrophoresis, Polyacrylamide Gel; Female; Frontal Lobe - enzymology; Frontal Lobe - metabolism; Frontal Lobe - pathology; Humans; Image Processing, Computer-Assisted; Isoenzymes; Male; Medical sciences; Nerve Tissue Proteins - metabolism; Neurodegenerative Diseases - enzymology; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurology; Original Research Article; Oxidative Stress; Parkinson Disease - enzymology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; Oxidative stress; Creatine kinase BB; Neurodegenerative disorders; Protein carbonyls; Human; Nervous system diseases; Frontal lobe; Enzyme; Creatine kinase; Transferases; Exploration; Cerebral disorder; Central nervous system disease; Degenerative disease; Comparative study; Brain (vertebrata)
• DOI: 10.1159/000017098
• ISSN: 1420-8008

The presence of the biomarkers of oxidative damage, protein carbonyl formation and the inactivation of oxidatively sensitive brain creatine kinase (CK BB, cytosolic isoform), were studied in frontal lobe autopsy specimens obtained from patients with different age-related neurodegenerative diseases: Alzheimer’s disease (AD), Pick’s disease (PkD), diffuse Lewy body disease (DLBD), Parkinson’s disease (PD), and age-matched control subjects. The CK activity was significantly reduced in the frontal lobe of AD, PkD and DLBD subjects, and CK BB-specific mRNA was significantly reduced in AD and DLBD. Protein carbonyl content was significantly increased in AD, PkD and DLBD. The results of this study confirm that the presence of biomarkers of oxidative damage is related to the presence of histopathological markers of neurodegeneration. Our data suggest that oxidative damage contributes to the development of the symptoms of frontal dysfunction in AD, PkD and DLBD. The development of frontal dysfunction in idiopathic PD might be secondary to oxidative damage and neuronal loss primarily located in the nigrostriatal system. The results of CK BB expression analysis demonstrate that the loss of the isoenzyme in different neurodegenerative diseases is likely the consequence of its posttranslational modification, possibly oxidative damage. Changes in CK BB expression may be an early indicator of oxidative stress in neurons.