title: 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.
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 lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 Å on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 Å. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 Å and 113 Å, while apoA-I-rHDL showed almost single band around 98 Å 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.
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea.|Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea.|BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Yoo
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea.|Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea.|BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Seung-Taek
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Sookmyung Women's University, Seoul 140-742, Korea.
authors.forename: Sihyun
authors.initials: S
authors.lastname: Ham
authors.affiliation: School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea.|Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Korea.|BK21plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Korea.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000502:physiology; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D001054:Apolipoproteins A / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D002942:Circular Dichroism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C505693:APOA1 protein, human; D000975:Antioxidants; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D010743:Phospholipids; C022205:apolipoprotein A-IV
keywords: apolipoprotein A-4; apolipoprotein A-I; fructosylation; recombinant high-density lipoprotein