title: The Application of Multiple Reaction Monitoring to Assess Apo A-I Methionine Oxidations in Diabetes and Cardiovascular Disease.
abstract: The oxidative modification of apolipoprotein A-I 's methionine148(M148) is associated with defective HDL function in vitro. Multiple Reaction Monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing oxidized M148 to the native peptide in Apo A-I. Measurement of the oxidized-to-unoxidized-M148 ratio was reproducible (CV<5%). The extent of methionine M148 oxidation in the HDL of healthy controls, and type 2 diabetic participants with and without prior cardiovascular events (CVD) were then examined. The results suggest a significant increase in the relative ratio of the peptide containing oxidized M148 to the unmodified peptide in the HDL of participants with diabetes and CVD (p<0.001), compared to participants without CVD. Monitoring the abundance ratio of the peptides containing oxidized and unoxidized M148 by MRM provides a means of examining the relationship between M148 oxidation and vascular complications in CVD.
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Hussein N
authors.initials: HN
authors.lastname: Yassine
authors.affiliation: University of Victoria - Genome British Columbia Proteomics Centre, Victoria, BC.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jackson
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.affiliation: Biodesign, Arizona State University, Tempe, AZ.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
authors.affiliation: Biodesign, Arizona State University, Tempe, AZ.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Nelson
authors.affiliation: Southwest Environmental Health Sciences Center, Tucson, AZ.
authors.forename: Serrine S
authors.initials: SS
authors.lastname: Lau
authors.affiliation: University of Victoria - Genome British Columbia Proteomics Centre, Victoria, BC ; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Borchers
keywords: Cardiovascular Disease; Diabetes; HDL; Multiple Reaction Monitoring; Proteomics