Increased methionine sulfoxide content of apoA-I 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, John W. Baynes

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41 Scopus citations

Abstract

Cardiovascular disease is a major cause of morbidity and premature mortality in diabetes. 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 (Met) residues in apolipoprotein A-I (apoA-I), 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 apoA-I of HDL isolated from plasma of healthy control and type 1 diabetic subjects to assess apoA-I exposure to lipid peroxides and the status of oxidative stress in the vascular compartment in diabetes. Three tryptic peptides of apoA-I contain Met residues: Q 84- M 86-K 88,W 108-M 112-R 116, and L 144-M 148-R 149. 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 (Met 86, Met 112, and Met 148) in diabetic patients. The increase in Met(O) in the diabetic group did not correlate with other biomarkers of oxidative stress, such as N ε-malondialde- hyde-lysine or N ε-(carboxymethyl)lysine, in plasma or lipoproteins. The higher Met(O) content in apoA-I from diabetic patients is consistent with increased levels of lipid peroxidation products in plasma in diabetes.

Original languageEnglish (US)
Pages (from-to)847-855
Number of pages9
JournalJournal of Lipid Research
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2008

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Keywords

  • Apolipoprotein A-I
  • High density lipoprotein
  • Oxidation
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Brock, J. W. C., Jenkins, A. J., Lyons, T. J., Klein, R. L., Yim, E., Lopes-Virella, M., Carter, R. E., Thorpe, S. R., & Baynes, J. W. (2008). Increased methionine sulfoxide content of apoA-I in type 1 diabetes. Journal of Lipid Research, 49(4), 847-855. https://doi.org/10.1194/jlr.M800015-JLR200