Bile acid transport in hypercholesterolemic resistant rabbits.
We examined bile acid transport and expression of the apical sodium-dependent bile acid transporter (ASBT) in ileal preparations to determine if alterations in bile acid excretion contributed to a hypercholesterolemia-resistant phenotype in rabbits (CRT/mlo). Taurocholate transport was not different between normal (NR) and CRT/mlo rabbits fed regular diet. However, feeding cholesterol-enriched diet reduced taurocholate transport significantly in CRT/mlo rabbits (0.53 + or - 0.06 pmol/microg protein) compared to regular diet (0.95 + or - 0.14 pmol/microg protein), but had no effect in NR rabbits. Cholesterol-enriched diet increased ASBT mRNA in CRT/mlo (2.6 + or - 0.7 to 5.4 + or - 0.1); no significant changes occurred in NR. Some CRT/mlo rabbits carry a polymorphism in ASBT at amino acid 333 (P333L). In transfected HEK293 cells, TC transport of P333L allele was significantly lower (0.08 + or - 0.01 vs 0.13 + or - 0.01 pmol/microg protein/15 sec, P< 0.05). This allele was not found in NR rabbits. The data suggest that the phenotype of the CRT/mlo rabbit is due to changes in bile acid transport as well as bile acid metabolism.
Izzat
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NN
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, USA.
Overturf
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M
Weisbrodt
N W
NW
Loose
D S
DS
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D011817:Rabbits; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D013656:Taurocholic Acid / Q000378:metabolism; D014162:Transfection
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D002784:Cholesterol