Biliary anionic peptide fraction and apoA-I regulate intestinal cholesterol uptake.
Evidence is now in favor of protein-facilitated mechanisms for the intestinal cholesterol absorption. Here we report that the unesterified cholesterol uptake by rat jejunal brush border membrane vesicles (BBMVs) is efficient, saturable, and protein-mediated. The human apolipoproteins biliary anionic peptide factor (APF) and A-I (apoA-I) up-regulate micellar cholesterol uptake in a dose-dependent manner, but for all tested concentrations (0.1-20 microM), the lipid-free APF was more efficient than apoA-I. This uptake stimulation was suppressed after addition of Pabs directed to the external lipid-binding domain of the CLA-1/SR-BI and reduced by Pabs directed to the external loop of CD36. Thus, CLA-1/SR-BI and to a lesser extent CD36 are involved in the regulation of intestinal cholesterol uptake. APF, the main protein bound to biliary lipids, is likely one of their physiological effectors. As APF is an unesterified cholesterol carrier, it could facilitate the intestinal absorption of biliary cholesterol.
Jourdheuil-Rahmani
Dominique
D
Unit 476-Human Nutrition and Lipids, National Institute for Health and Medical Research (INSERM), Marseille, France. Dominique.Jourdheuil-Rahmani@pharmacie.univ-mrs.fr
Charbonnier
Monique
M
Domingo
Nicole
N
Luccioni
François
F
Lafont
Huguette
H
Lairon
Denis
D
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001059:Apoproteins / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D016632:Apolipoprotein A-I; D001059:Apoproteins; D002135:Calcium-Binding Proteins; D018110:Receptors, Lipoprotein; C489588:anionic polypeptide fraction, human; C076065:anionic polypeptide fraction, rat; D002784:Cholesterol