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Glycation of paraoxonase‐1 inhibits its activity and impairs the ability of high‐density lipoprotein to metabolize membrane lipid hydroperoxides
Author(s) -
Mastorikou M.,
Mackness B.,
Liu Y.,
Mackness M.
Publication year - 2008
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2008.02546.x
Subject(s) - pon1 , glycation , paraoxonase , medicine , endocrinology , type 2 diabetes , lipoprotein , diabetes mellitus , cholesterol , high density lipoprotein , low density lipoprotein , oxidative stress , biochemistry , chemistry , genotype , gene
Aims High‐density lipoprotein (HDL) protects against atherosclerosis development. Defective functioning of HDL in Type 2 diabetes may be one cause of increased cardiovascular disease associated with Type 2 diabetes. HDL modulates low‐density lipoprotein and cell membrane oxidation through the action of paraoxonase‐1 (PON1), which is one of the major mechanisms by which HDL is anti‐atherogenic. Methods We have compared the ability of HDL from Type 2 diabetic patients without coronary heart disease (CHD) ( n = 36) to metabolize membrane lipid hydroperoxides with HDL from healthy control subjects ( n = 19) and people with CHD but no diabetes ( n = 37). Results HDL from subjects with Type 2 diabetes and CHD metabolized 20% less membrane hydroperoxides than HDL from control subjects ( P < 0.05). The PON1‐192RR was least efficient in all the study groups. PON1 was glycated in vivo : (7.5% control, 12% CHD, 17% Type 2 diabetes P < 0.01) with QQ isoforms most glycated. In vitro glycation of PON1 reduced its ability to metabolize membrane hydroperoxides by 50% ( P < 0.001); however, glyoxidation reduced it by 80% ( P < 0.001). In the control group only there was a significant negative correlation between PON1 activity and the ability of HDL to metabolize membrane hydroperoxides ( r = −0.911, P < 0.001). Conclusions HDL from Type 2 diabetic patients without CHD has decreased ability to metabolize membrane lipid hydroperoxides, which could lead to increased susceptibility to cardiovascular disease.