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KMID : 0578320150380060573
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Molecules and Cells
2015 Volume.38 No. 6 p.573 ~ p.579
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Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity
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Yoo Jeong-Ah
Lee Eun-Young
Park Ji-Yoon
Lee Seung-Taek
Ham Si-Hyun
Cho Kyung-Hyun
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Abstract
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Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 ? on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 ?. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 ? and 113 ?, while apoA-I-rHDL showed almost single band around 98 ? size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, BS3-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties.
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KEYWORD
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apolipoprotein A-I, apolipoprotein A-4, fructosylation, recombinant high-density lipoprotein
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