HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress

Xenia Moren, Sara P. Deakin, Ming-Lin Liu, Marja-Riitta Taskinen, and Richard W. James

Endocrinology, Diabetes and Nutrition, Geneva University Medical School, Geneva 11 1211

Corresponding Author: Richard.James{at}hcuge.ch

The subfraction distribution of HDL-associated peptides has implications for their functions and the impact of pathological modifications to lipoprotein metabolism on these functions. We have analyzed the subfraction distribution of paraoxonase-1 (PON1) and the consequences for enzyme activity and stability. HDL subfractions were defined by the presence (LpAI,AII) or absence (LpAI) of apolipoprotein AII. PON1 was present in both subfractions, although increased concentrations of HDL were associated with significantly increased PON1 in LpAI. ApoAII did not modify the capacity of native, human HDL or reconstituted HDL to promote PON1 secretion from cells or stabilize enzyme activity. Neither did apoAII decrease PON1 activity when added to rabbit serum normally devoid of the apolipoprotein. LpAI,AII particles isolated from human serum or reconstituted HDL(LpAI,AII) showed a significantly greater capacity than HDL(LpAI) to stabilize secreted PON1 and purified, recombinant PON1 added to such particles. PON1 associated with apoAII containing particles showed greater resistance to inactivation arising from oxidation. ApoAI, apoAII and LpAI,AII, but not LpAI, were independent determinants of serum PON1 concentration and activity in multivariate analyses. PON1 is at least equally distributed between LpAI and LpAII,AII HDL particles. This dichotomous distribution has implications for PON1 activity and stability that may impact on the physiological role of the enzyme.

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