ApoE induces serum paraoxonase PON1 activity and stability similar to ApoA-I.
Serum paraoxonase (PON1) is an anti-atherogenic interfacially activated lipo-lactonase that was shown to selectively bind high-density lipoprotein (HDL) carrying apolipoprotein A-I (apoA-I). ApoA-I binding occurs with nanomolar affinity and induces a dramatic increase in enzyme stability and lactonase activity. This study examined the association of PON1 with reconstituted HDL (rHDL) carrying apolipoprotein E, and its consequences on the stability and enzymatic activity of PON1, and on its anti-atherogenic potential. The results indicate that reconstituted HDL particles prepared with two most common isoforms of apoE (apoE3 and apoE4) associate with rePON1 in a manner and affinity similar to those of apoA-I. Binding to apoE-HDL stimulates the lactonase activity and stabilizes the enzyme, although the latter occurs to a >10-fold lesser extent compared to apoA-I-HDL particles. The anti-atherogenic potential of PON1, measured by inhibition of LDL oxidation and stimulation of macrophage cholesterol efflux, was also stimulated by apoE-HDL, at levels of 40-96% compared to apoA-I-HDL. Overall, reconstituted apoE-HDL exhibits properties similar to those of apoA-I-HDL, but with a lower capacity to stabilize PON1 and to induce its anti-atherogenic functions. ApoE, apoA-I, and to a lesser degree apoA-IV show distinct structural and functional similarities but little sequence homology. That these apolipoproteins, but not apoA-II, bind PON1 with high affinity and stimulate its activity suggests that PON1-HDL recognition is based primarily on surface properties of the apolipoproteins and that specific protein-protein interactions may play only a secondary role.
Gaidukov
Leonid
L
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Viji
R I
RI
Yacobson
Shiri
S
Rosenblat
Mira
M
Aviram
Michael
M
Tawfik
Dan S
DS
D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D004795:Enzyme Stability; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D043303:Aryldialkylphosphatase