Analysis of the acrolein-modified sites of apolipoprotein B-100 in LDL

Mizuki Kobayashi, Kenta Watanabe, Takehiro Suzuki, Naoshi Dohmae, Masachika Fujiyoshi, Masashi Uchida, Takaaki Suzuki, Kazuei Igarashi, Itsuko Ishii

Research output: Contribution to journalArticlepeer-review

Abstract

We have reported that acrolein-conjugated low-density lipoprotein (Acro-LDL) uptake by scavenger receptor class A type 1 (SR-A1) can mediate macrophage foam cell formation. The purpose of this study was to determine which amino acid residues of apoB protein in LDL are conjugated with acrolein. Acro-apoB was prepared by incubation of LDL with acrolein (10 to 60 μM) at 37 °C for 7 days. Identification of acrolein-conjugated amino acid residues in apoB was performed using LC-MS/MS. The levels of acrolein-conjugated amino acid residues of apoB as well as crosslinking apoB increased in proportion to acrolein concentration. The level of LDL uptake by macrophages was parallel with the acrolein-conjugated monomer apoB. Acrolein-conjugated amino acid residues in apoB were C212, K327, K742, K949, K1087, H1923, K2634, K3237 and K3846. The NH2-teriminal four amino acid residues (C212, K327, K742 and K949) were located at the scavenger receptor SR-A1 recognition site, suggesting that these four acrolein-conjugated amino acids are involved in the rapid uptake of Acro-LDL by macrophages. It is proposed that the rapid uptake of LDL by macrophages is dependent on acrolein conjugation of four amino acids residues at the scavenger receptor recognition site of apoB in LDL.

Original languageEnglish
Article number158809
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1866
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Acrolein
  • Apolipoprotein B-100
  • LDL
  • Mass spectrometry

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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