Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta(1-42): implications for Alzheimer's disease.
Protein oxidation has been shown to lead to loss of protein function, increased protein aggregation, decreased protein turnover, decreased membrane fluidity, altered cellular redox poteintial, loss of Ca2+ homeostaisis, and cell death. There is increasing evidence that protein oxidation is involved in the pathogenesis of Alzheimer's disease and amyloid beta-peptide (1-42) has been implicated as a mediator of oxidative stress in AD. However, the specific implications of the oxidation induced by Abeta(1-42) on the neurodegeneration evident in AD are unknown. In this study, we used proteomic techniques to identify specific targets of oxidation in transgenic Caenorhabditis elegans (C. elegans) expressing human Abeta(1-42). We identified 16 oxidized proteins involved in energy metabolism, proteasome function, and scavenging of oxidants that are more oxidized compared to control lines. These results are discussed with reference to Alzheimer's disease.
Boyd-Kimball
Debra
D
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, 121 Chemistry-Physics Building, University of Kentucky, Lexington, KY 40506-0055, USA.
Poon
H Fai
HF
Lynn
Bert C
BC
Cai
Jian
J
Pierce
William M
WM
Klein
Jon B
JB
Ferguson
Jmil
J
Link
Christopher D
CD
Butterfield
D Allan
DA
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western / Q000379:methods; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D040901:Proteomics / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods
D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)