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标题：Increased methionine sulfoxide content of apoA-I in type 1 diabetes
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作者：Jonathan W. C. Brock ; Alicia J. Jenkins ; Timothy J. Lyons 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：4
页码：847-855
DOI：10.1194/jlr.M800015-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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: 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 ^ϵ-malondialdehyde-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. Using the methods developed here, future studies can address the relationship between Met(O) in apoA-I and the risk, development, or progression of the vascular complications of diabetes.