The current address for B. and M. Mackness is PONTECH, 27 Cote Green Road, Marple Bridge, Stockport SK6 5EW, UK.
Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high-density lipoprotein to metabolize membrane lipid hydroperoxides
Article first published online: 29 AUG 2008
© 2008 The Authors. Journal compilation © 2008 Diabetes UK
Volume 25, Issue 9, pages 1049–1055, September 2008
How to Cite
Mastorikou, M., Mackness, B., Liu, Y. and Mackness, M. (2008), Glycation of paraoxonase-1 inhibits its activity and impairs the ability of high-density lipoprotein to metabolize membrane lipid hydroperoxides. Diabetic Medicine, 25: 1049–1055. doi: 10.1111/j.1464-5491.2008.02546.x
- Issue published online: 29 AUG 2008
- Article first published online: 29 AUG 2008
- Accepted 4 July 2008
- coronary heart disease;
- lipid hydroperoxides;
- Type 2 diabetes
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.