Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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

  • Yoo, Jeong-Ah (School of Biotechnology, Yeungnam University) ;
  • Lee, Eun-Young (School of Biotechnology, Yeungnam University) ;
  • Park, Ji Yoon (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Lee, Seung-Taek (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University) ;
  • Ham, Sihyun (Department of Chemistry, Sookmyung Women's University) ;
  • Cho, Kyung-Hyun (School of Biotechnology, Yeungnam University)
  • Received : 2015.02.23
  • Accepted : 2015.03.18
  • Published : 2015.06.30
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Abstract

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 lipidbound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and $67{\AA}$ on native gel electrophoresis, while apoA-I showed scattered band pattern less than $71{\AA}$. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around $101{\AA}$ and $113{\AA}$, while apoA-I-rHDL showed almost single band around $98{\AA}$ size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, $BS_3$-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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References

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