Apolipoprotein J Is Associated with Paraoxonase in Human Plasma

Abstract

Apolipoprotein J (apoJ)-containing high-density lipoproteins (HDL), isolated from human plasma by immunoaffinity chromatography, are associated with apoAI and a protein of approximately 44 kDa. In order to advance our understanding of apoJ's role in the vasculature, a comprehensive investigation was performed to identify and characterize this 44-kDa protein and to study its interaction with apoJ. The 44-kDa protein, a monomeric glycoyslated polypeptide, was identified by N-terminal sequencing as serum paraoxonase. Paraoxonase exists in two oxidation states: one contains all free cysteines while the other has one disulfide bond between Cys42 and Cys284. Northern analysis of eight human tissues shows paraoxonase message present only in the liver. The majority of apoJ/paraoxonase-HDL are 90-140 kDa; however, not all of the plasma paraoxonase is associated with apoJ. The specificity of the apoJ/paraoxonase interaction, inferred by the constant mole ratio of the two proteins in affinity-purified apoJ-HDL, is confirmed in direct binding assays. For purified proteins, there is more than a 5-fold increase in the apparent affinity of apoJ for immobilized paraoxonase as the paraoxonase coating concentration is increased from 0.5 to 2.0 micrograms/mL. Both oxidation states of paraoxonase bind to apoJ with equal affinity. Our data combined with other evidence suggest that the plasma link of apoJ with paraoxonase will be implicated as a predictor of vascular damage.

Rabbit Serum Paraoxonase 3 (PON3) Is a High Density Lipoprotein-associated Lactonase and Protects Low Density Lipoprotein against Oxidation

“…3 and Table IV). Immunopurified PON1 is associated with two major proteins: apoA-I and apoJ (30,31), but PON3 seems to be more widely distributed than PON1 in the gel filtration HDL fractions (Fig. 3).…”

Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes.

“…In serum, paraoxonase appears to be restricted to and thus active within HDL particles. There is usually a defined stoichiometry concerning the apolipoproteins present in HDL complexes (30)(31)(32). If there is a defined number of paraoxonase molecules per HDL particle, activity of HDL containing B or L alleles will be less than that of HDL containing A or M alleles.…”

N-(2-Oxo-3-oxetanyl)carbamic Acid Esters as N-Acylethanolamine Acid Amidase Inhibitors: Synthesis and Structure–Activity and Structure–Property Relationships

“…66 In that case, a potential application of these compounds as "soft drugs" for the treatment of asthma was postulated, 67 based on the nonubiquitous distribution of paraoxonase, and in particular on its absence from the lung tissue. 61 Soft drugs exert their therapeutic action in the target tissue and are then converted into inactive metabolites upon reaching the systemic circulation. In the literature, the soft drug strategy has been successfully exploited for topically applied drugs.…”