Home Life Sciences N-homocysteinylation of apolipoprotein A-I impairs the protein’s antioxidant ability but not its cholesterol efflux capacity
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N-homocysteinylation of apolipoprotein A-I impairs the protein’s antioxidant ability but not its cholesterol efflux capacity

  • Akari Miyazaki , Nozomi Sagae , Yoko Usami , Megumi Sato , Takahiro Kameda , Akira Yoshimoto , Nau Ishimine , Kazuyuki Matsuda , Mitsutoshi Sugano , Masayuki Hara , Takayuki Honda and Minoru Tozuka EMAIL logo
Published/Copyright: February 14, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 395 Issue 6

Abstract

A high homocysteine (Hcy) level is a risk factor for atherosclerosis. Hcy can be added to proteins through a process known as N-homocysteinylation. This is thought to be a potential cause of atherosclerosis induction. We previously reported that N-homocysteinylated apolipoprotein A-I (N-Hcy-apoA-I) was identified in normal human plasma. In this study, the effect of N-homocysteinylation on the functions of apoA-I was examined. A kinetic study using dimyristoyl phosphatidylcholine (DMPC) liposomes indicated that N-Hcy-apoA-I showed increased lipid-binding activity compared to wild-type apoA-I. Two reconstituted high-density lipoprotein (rHDL) particles of different sizes (approximately 8.2 nm and 7.6 nm in diameter) were produced by mixing apoA-I and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). However, an increased ratio of large to small particles was found in rHDL prepared with N-Hcy-apoA-I. The normal apoA-I antioxidant ability, estimated by the suppression of conjugated diene formation in low-density lipoprotein (LDL) induced by copper sulfate oxidation, was considerably impaired when using N-Hcy-apoA-I. Although N-Hcy-apoA-I functioned as an oxidant, no significant difference was observed in the cholesterol efflux capacity from THP-1 macrophages between wild-type apoA-I and N-Hcy-apoA-I. These results suggest that N-Hcy-apoA-I might be proatherogenic due to its oxidative behavior but not an attenuation of cholesterol efflux capacity.

Keywords: antioxidant ability; cholesterol efflux; DMPC clearance; homocysteine; N-homocysteinylated apoA-I; THP1 cells
Corresponding author: Minoru Tozuka, Analytical Laboratory Chemistry, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan, e-mail:

Acknowledgments

We thank Professor Tetsuo Kubota (Microbiology and Immunology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University) for generously assisting our collaborators. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant number 21590611).

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Received: 2013-9-29
Accepted: 2014-2-10
Published Online: 2014-2-14
Published in Print: 2014-6-1

©2014 by Walter de Gruyter Berlin/Boston

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https://doi.org/10.1515/hsz-2013-0262
Keywords for this article
antioxidant ability; cholesterol efflux; DMPC clearance; homocysteine; N-homocysteinylated apoA-I; THP1 cells

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes
  4. Human dyskerin: beyond telomeres
  5. Assembly and function of small RNA – Argonaute protein complexes
  6. Minireview
  7. The globin superfamily: functions in nitric oxide formation and decay
  8. Research Articles/Short Communications
  9. Protein Structure and Function
  10. N-homocysteinylation of apolipoprotein A-I impairs the protein’s antioxidant ability but not its cholesterol efflux capacity
  11. Lucimycin, an antifungal peptide from the therapeutic maggot of the common green bottle fly Lucilia sericata
  12. A lysine-methionine exchange in a coronavirus surface protein transforms a retention motif into an endocytosis signal
  13. Cell Biology and Signaling
  14. Upregulation of the thioredoxin-dependent redox system during differentiation of 3T3-L1 cells to adipocytes
  15. Novel Techniques
  16. Shortening distance of forward and reverse primers for nucleic acid isothermal amplification
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