Increased methionine sulfoxide content of apoai in type 1 diabetes

Jonathan W. C.. Brock, Alicia J. Jenkins, Timothy J. Lyons, Richard L. Klein, Eunsil Yim, Maria Lopes-Virella, Rickey E. Carter, Suzanne R. Thorpe, and John W. Baynes

Exercise Science, University of South Carolina, Columbia, SC 29208

Corresponding Author: john.baynes{at}sc.edu

Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. High density lipoprotein (HDL) plays an important role in limiting vascular damage by removing cholesterol and cholesteryl ester hydroperoxides from oxidized low density lipoprotein and foam cells. Methionine residues in ApoAI, the major apolipoprotein of HDL, reduce peroxides in HDL lipids, forming methionine sulfoxide [Met(O)]. We examined the extent and sites of Met(O) formation in ApoAI of HDL isolated from plasma of healthy control and type 1 diabetic subjects in order to assess ApoAI exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of ApoAI contain methionine residues: Q84-M86-K88, W108-M112-R116 and L144-M148-R149. These peptides and their Met(O) analogs were identified and quantified by mass spectrometry. Relative to controls, Met(O) formation was significantly increased at all three locations (Met86, Met112 and Met148) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N-malondialdehyde-lysine or N-(carboxymethyl)lysine in plasma or lipoproteins. The higher Met(O) content in ApoAI from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes. Using the methods developed here, future studies can address the relationship between Met(O) in ApoAI and risk, development or progression of the vascular complications of diabetes.

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