The Experts below are selected from a list of 147324 Experts worldwide ranked by ideXlab platform
Allan D Butterfield - One of the best experts on this subject based on the ideXlab platform.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part ii dihydropyrimidinase related protein 2 α enolase and heat shock cognate 71
Journal of Neurochemistry, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In Particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control Brain, suggesting a possible role for oxidation-related decrease in protein function in the process of neurodegeneration. Oxidative damage to proteins, assessed by measuring the protein carbonyl content, is involved in several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, neuronal death. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. Previously, we used our proteomics approach, which successfully substitutes for labor-intensive immunochemical analysis, to detect proteins and identified creatine kinase, glutamine synthase and ubiquitin carboxy-terminal hydrolase L−1 as specifically oxidized proteins in AD Brain. In this report we again applied our proteomics approach to identify new targets of protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase related protein 2 (DRP-2), which is involved in the axonal growth and guidance, showed significantly increased level in protein carbonyls in AD Brain, suggesting a role for impaired mechanism of neural network formation in AD. Additionally, the cytosolic enzyme α-enolase was identified as a target of protein oxidation and is involved the glycolytic pathway in the pathological events of AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not significant, oxidation in AD Brain. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Abstract Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and β-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer’s disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and beta-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer's disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
Alessandra Castegna - One of the best experts on this subject based on the ideXlab platform.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part ii dihydropyrimidinase related protein 2 α enolase and heat shock cognate 71
Journal of Neurochemistry, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In Particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control Brain, suggesting a possible role for oxidation-related decrease in protein function in the process of neurodegeneration. Oxidative damage to proteins, assessed by measuring the protein carbonyl content, is involved in several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, neuronal death. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. Previously, we used our proteomics approach, which successfully substitutes for labor-intensive immunochemical analysis, to detect proteins and identified creatine kinase, glutamine synthase and ubiquitin carboxy-terminal hydrolase L−1 as specifically oxidized proteins in AD Brain. In this report we again applied our proteomics approach to identify new targets of protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase related protein 2 (DRP-2), which is involved in the axonal growth and guidance, showed significantly increased level in protein carbonyls in AD Brain, suggesting a role for impaired mechanism of neural network formation in AD. Additionally, the cytosolic enzyme α-enolase was identified as a target of protein oxidation and is involved the glycolytic pathway in the pathological events of AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not significant, oxidation in AD Brain. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Abstract Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and β-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer’s disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and beta-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer's disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
Dennis L Kolson - One of the best experts on this subject based on the ideXlab platform.
-
age related total gray matter and white matter changes in normal adult Brain Part i volumetric mr imaging analysis
American Journal of Neuroradiology, 2002Co-Authors: Robert I Grossman, James S Babb, Marcie L Rabin, Lois J Mannon, Dennis L KolsonAbstract:BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human Brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20–86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (≥50 years) than in younger subjects ( CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of Brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process.
-
age related total gray matter and white matter changes in normal adult Brain Part i volumetric mr imaging analysis
American Journal of Neuroradiology, 2002Co-Authors: Yulin Ge, Robert I Grossman, James S Babb, Marcie L Rabin, Lois J Mannon, Dennis L KolsonAbstract:BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and total white matter (WM) in human Brain is now available. We investigated the effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM) volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four healthy volunteers (22 men, 32 women) aged 20–86 years underwent dual-echo fast spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were segmented by using MR image-based computerized semiautomated software. Volumes were normalized as a percentage of intracranial volume (%GM and %WM) to adjust for variations in head size. Age and sex effects were then assessed. RESULTS: Both %GM and %WM in the intracranial space were significantly less in older subjects (≥50 years) than in younger subjects ( P P = .02, respectively). Consistently, %GM decreased linearly with age, beginning in the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate beginning only in adult midlife. Although larger GM volumes were observed in men before adjustments for cranium size, no significant differences in %GM or %WM were observed between the sexes. CONCLUSION: GM volume loss appears to be a constant, linear function of age throughout adult life, whereas WM volume loss seems to be delayed until middle adult life. Both appear to be independent of sex. Quantitative analysis of %GM and %WM volumes can improve our understanding of Brain atrophy due to normal aging; this knowledge may be valuable in distinguishing atrophy of disease patterns from characteristics of the normal aging process.
-
age related total gray matter and white matter changes in normal adult Brain Part ii quantitative magnetization transfer ratio histogram analysis
American Journal of Neuroradiology, 2002Co-Authors: Robert I Grossman, James S Babb, Marcie L Rabin, Lois J Mannon, Dennis L KolsonAbstract:BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and quantitative identifier of underlying structural changes in the Brain. We quantitatively evaluated age- and sex-related MTR changes in global gray matter (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy volunteers (21 men, 31 women) aged 20–86 years underwent dual-echo fast spin-echo and magnetization transfer imaging performed with and then without a saturation pulse. GM and WM were distinguished by using a computer-assisted semiautomated segmentation technique. MTR histograms were generated for each segmented tissue in each subject and compared among age and sex groups. RESULTS: The mean, median, first quartile, and peak height of the MTR histogram were significantly lower in the older group (≥50 years) than those in the younger group ( CONCLUSION: The different MTR values for both GM and WM in the two age groups suggest that notable microscopic changes occur in GM and WM with advancing age, yet no significant sex-related variations in MTR measurements were found in these neurologically healthy adults. Such normative data based on the inherent contrast in MTRs are essential in studies of specific disorders of aging, and they may have implications for our understanding of the gross structural changes in both GM and WM in the aging Brain.
Michael Y Aksenov - One of the best experts on this subject based on the ideXlab platform.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part ii dihydropyrimidinase related protein 2 α enolase and heat shock cognate 71
Journal of Neurochemistry, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In Particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control Brain, suggesting a possible role for oxidation-related decrease in protein function in the process of neurodegeneration. Oxidative damage to proteins, assessed by measuring the protein carbonyl content, is involved in several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, neuronal death. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. Previously, we used our proteomics approach, which successfully substitutes for labor-intensive immunochemical analysis, to detect proteins and identified creatine kinase, glutamine synthase and ubiquitin carboxy-terminal hydrolase L−1 as specifically oxidized proteins in AD Brain. In this report we again applied our proteomics approach to identify new targets of protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase related protein 2 (DRP-2), which is involved in the axonal growth and guidance, showed significantly increased level in protein carbonyls in AD Brain, suggesting a role for impaired mechanism of neural network formation in AD. Additionally, the cytosolic enzyme α-enolase was identified as a target of protein oxidation and is involved the glycolytic pathway in the pathological events of AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not significant, oxidation in AD Brain. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Abstract Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and β-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer’s disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and beta-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer's disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
Visith Thongboonkerd - One of the best experts on this subject based on the ideXlab platform.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part ii dihydropyrimidinase related protein 2 α enolase and heat shock cognate 71
Journal of Neurochemistry, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder in which oxidative stress has been implicated as an important event in the progression of the pathology. In Particular, it has been shown that protein modification by reactive oxygen species (ROS) occurs to a greater extent in AD than in control Brain, suggesting a possible role for oxidation-related decrease in protein function in the process of neurodegeneration. Oxidative damage to proteins, assessed by measuring the protein carbonyl content, is involved in several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, neuronal death. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. Previously, we used our proteomics approach, which successfully substitutes for labor-intensive immunochemical analysis, to detect proteins and identified creatine kinase, glutamine synthase and ubiquitin carboxy-terminal hydrolase L−1 as specifically oxidized proteins in AD Brain. In this report we again applied our proteomics approach to identify new targets of protein oxidation in AD inferior parietal lobe (IPL). The dihydropyrimidinase related protein 2 (DRP-2), which is involved in the axonal growth and guidance, showed significantly increased level in protein carbonyls in AD Brain, suggesting a role for impaired mechanism of neural network formation in AD. Additionally, the cytosolic enzyme α-enolase was identified as a target of protein oxidation and is involved the glycolytic pathway in the pathological events of AD. Finally, the heat shock cognate 71 (HSC-71) revealed increased, but not significant, oxidation in AD Brain. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Abstract Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and β-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer’s disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.
-
proteomic identification of oxidatively modified proteins in alzheimer s disease Brain Part i creatine kinase bb glutamine synthase and ubiquitin carboxy terminal hydrolase l 1
Free Radical Biology and Medicine, 2002Co-Authors: Alessandra Castegna, Michael Y Aksenov, Marina V Aksenova, Visith Thongboonkerd, Jon B Klein, William M Pierce, Rosemarie M Booze, William R Markesbery, Allan D ButterfieldAbstract:Oxidative alterations of proteins by reactive oxygen species (ROS) have been implicated in the progression of aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD). Protein carbonyls, a marker of protein oxidation, are increased in AD Brain, indicating that oxidative modification of proteins is relevant in AD. Oxidative damage can lead to several events such as loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, and, ultimately, to neuronal death. Identification of specific targets of protein oxidation represents a crucial step in establishing a relationship between oxidative modification and neuronal death in AD, and was Partially achieved previously in our laboratory through immunochemical detection of creatine kinase BB and beta-actin as specifically oxidized proteins in AD Brain versus control Brain. However, this process is laborious, requires the availability of specific antibodies, and, most importantly, requires a reasonable guess as to the identity of the protein in the first place. In this study, we present the first proteomics approach to identify specifically oxidized proteins in AD, by coupling 2D fingerprinting with immunological detection of carbonyls and identification of proteins by mass spectrometry. The powerful techniques, emerging from application of proteomics to neurodegenerative disease, reveal the presence of specific targets of protein oxidation in Alzheimer's disease (AD) Brain: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD Brain. Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method.