Cyclosporin A Traps ABCA1 at the Plasma Membrane and Inhibits ABCA1-Mediated Lipid Efflux to Apolipoprotein A-I - Archive ouverte HAL
Article Dans Une Revue Arteriosclerosis, Thrombosis, and Vascular Biology Année : 2004

Cyclosporin A Traps ABCA1 at the Plasma Membrane and Inhibits ABCA1-Mediated Lipid Efflux to Apolipoprotein A-I

Dao-Quan Peng
  • Fonction : Auteur
Megan Settle
  • Fonction : Auteur
Gregory Brubaker
  • Fonction : Auteur
Richard Morton
  • Fonction : Auteur
Jonathan Smith
  • Fonction : Auteur

Résumé

Objective— ABCA1 mediates cellular cholesterol and phospholipid efflux to apolipoprotein A-I and other apolipoprotein acceptors. In this study, we analyzed the effect of the immunosuppressant cyclosporin A on the ABCA1-mediated lipid effluxes reactions. Methods and Results— Cyclosporin A acted as a potent inhibitor of ABCA1 activity in several cell lines. Using the RAW264.7 mouse macrophage cell line, in which ABCA1 and its associated cholesterol efflux activity are inducible by cAMP analogues, cyclosporin A inhibition of cholesterol efflux to apolipoprotein A-I was rapidly reversible after its removal from the culture media, implying that ABCA1 levels were not drastically reduced by cyclosporin A. In fact, cyclosporin A treatment decreased ABCA1 turnover and yielded a 2-fold increase in cell-surface ABCA1. Despite the increase in cell-surface ABCA1, cyclosporin A decreased apolipoprotein A-I uptake, resecretion, and degradation in RAW cells. Finally, consistent with the inhibition of ABCA1 in vitro, cyclosporin A treatment induced a 33% reduction of high-density lipoprotein (HDL) levels in mice. Conclusion— ABCA1 inhibition by cyclosporin A supports a role for ABCA1 endocytic trafficking in ABCA1-mediated lipid efflux and could explain in part the low HDL levels observed in some patients with transplants.

Dates et versions

hal-03624813 , version 1 (30-03-2022)

Identifiants

Citer

Wilfried Le Goff, Dao-Quan Peng, Megan Settle, Gregory Brubaker, Richard Morton, et al.. Cyclosporin A Traps ABCA1 at the Plasma Membrane and Inhibits ABCA1-Mediated Lipid Efflux to Apolipoprotein A-I. Arteriosclerosis, Thrombosis, and Vascular Biology, 2004, 24 (11), pp.2155-2161. ⟨10.1161/01.ATV.0000144811.94581.52⟩. ⟨hal-03624813⟩
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