HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress.
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 (LpA-I,A-II) or absence (LpA-I) of apolipoprotein A-II (apoA-II). PON1 was present in both subfractions, although increased concentrations of HDL were associated with significantly increased PON1 in LpA-I. ApoA-II did not modify the capacity of native human HDL or reconstituted HDL to promote PON1 secretion from cells or to stabilize enzyme activity, nor did apoA-II decrease PON1 activity when added to rabbit serum normally devoid of the apolipoprotein. LpA-I,A-II particles isolated from human serum or reconstituted HDL (LpA-I,A-II) showed a significantly greater capacity than HDL(LpA-I) to stabilize secreted PON1 and purified recombinant PON1 added to such particles. PON1 associated with apoA-II-containing particles showed greater resistance to inactivation arising from oxidation. ApoA-I, apoA-II, and LpA-I,A-II, but not LpA-I, were independent determinants of serum PON1 concentration and activity in multivariate analyses. PON1 is at least equally distributed between LpA-I and LpA-II,A-II HDL particles. This dichotomous distribution has implications for PON1 activity and stability that may impact on the physiological role of the enzyme.
Moren
Xenia
X
Clinical Diabetes Unit, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Deakin
Sara
S
Liu
Ming-Lin
ML
Taskinen
Marja-Riitta
MR
James
Richard W
RW
D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D016466:CHO Cells; D002853:Chromatography, Liquid; D006224:Cricetinae; D003412:Cricetulus; D004795:Enzyme Stability; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D018384:Oxidative Stress
D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase