Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL

Anny Mulya, Ji Young Lee, Abraham K. Gebre, Elena Y. Boudyguina, Soon Kyu Chung, Thomas L. Smith, Perry L. Colvin, Xian Cheng Jiang, John S. Parks

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

We investigated the in vivo metabolic fate of pre-β HDL particles in human apolipoprotein A-I transgenic (hA-ITg) mice. Pre-β HDL tracers were assembled by incubation of [125I]tyramine cellobiose-labeled apolipoprotein A-I (apoA-I) with HEK293 cells expressing ABCA1. Radiolabeled pre-β HDLs of increasing size (pre-β1, -2, -3, and -4 HDLs) were isolated by fast-protein liquid chromatography and injected into hA-ITg-recipient mice, after which plasma decay, in vivo remodeling, and tissue uptake were monitored. Pre-β2, -3, and -4 had similar plasma die-away rates, whereas pre-β1 HDL was removed 7-fold more rapidly. Radiolabel recovered in liver and kidney 24 h after tracer injection suggested increased (P < 0.001) liver and decreased kidney catabolism as pre-β HDL size increased. In plasma, pre-β1 and -2 were rapidly (<5 min) remodeled into larger HDLs, whereas pre-β3 and -4 were remodeled into smaller HDLs. Pre-β HDLs were similarly remodeled in vitro with control or LCAT-immunodepleted plasma, but not when incubated with phospholipid transfer protein knockout plasma. Our results suggest that initial interaction of apoA-I with ABCA1 imparts a unique conformation that partially determines the in vivo metabolic fate of apoA-I, resulting in increased liver and decreased kidney catabolism as pre-β HDL particle size increases.

Original languageEnglish (US)
Pages (from-to)2390-2401
Number of pages12
JournalJournal of Lipid Research
Volume49
Issue number11
DOIs
StatePublished - 2008

Keywords

  • ABCA1 transporter
  • Apolipoprotein A-I
  • High density lipoproteins
  • In vivo catabolism
  • Lecithin:cholesterol acyltransferase
  • Phospholipid transfer protein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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