Browsing by Author "Shneider, BL"
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- ItemIleal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits(LIPID RESEARCH INC, 2000) Xu, GR; Shneider, BL; Shefer, S; Nguyen, LB; Batta, AK; Tint, GS; Arrese, M; Thevananther, S; Ma, L; Stengelin, S; Kramer, W; Greenblatt, D; Pcolinsky, M; Salen, GWe investigated the effect of heal bile acid transport on the regulation of classic and alternative bile acid synthesis in cholesterol-fed rats and rabbits. Bile acid pool sizes, fecal bile acid outputs (synthesis rates), and the activities of cholesterol 7 alpha-hydroxylase (classic bile acid synthesis) and cholesterol 27-hydroxylase (alternative bile acid synthesis) were related to heal bile acid transporter expression (ileal apical sodium-dependent bile acid transporter, ASBT). Plasma cholesterol levels rose 2.1-times in rats (98 +/- 19 mg/dl) and 31-times (986 +/- 188 mg/dl) in rabbits. The bile acid pool size remained constant (55 +/- 17 mg vs. 61 +/- 18 mg) in rats but doubled (254 +/- 46 to 533 +/- 53 mg) in rabbits. ASBT protein expression did not change in rats but rose 31% (P < 0.05) in rabbits, Fecal bile acid outputs that reflected bile acid synthesis increased 2- and 2.4-times (P < 0.05) in cholesterol-fed rats and rabbits, respectively. Cholesterol 7 alpha-hydroxylase activity rose 33% (24 +/- 2.4 vs. 18 +/- 1.6 pmol/mg/min, P < 0.01) and mRNA levels increased 50% (P < 0.01) in rats but decreased 68% and 79%, respectively, in cholesterol-fed rabbits. Cholesterol 27-hydroxylase activity remained unchanged in rats but rose 62% (P < 0.05) in rabbits. Classic bile acid synthesis (cholesterol 7 alpha-hydroxylase) was inhibited in rabbits because an enlarged bile acid pool developed from enhanced ileal bile acid transport. In contrast, in rats, cholesterol 7 alpha-hydroxylase was stimulated but the bile acid pool did not enlarge because ASBT did not change. jlr Therefore, although bile acid synthesis was increased via different pathways in rats and rabbits, enhanced ileal bile acid transport was critical for enlarging the bile acid pool size that exerted feedback regulation on cholesterol 7 alpha-hydroxylase in rabbits.
- ItemMolecular analysis of the adaptive response of intestinal bile acid transport after ileal resection in the rat(W B SAUNDERS CO-ELSEVIER INC, 1998) Coppola, CP; Gosche, JR; Arrese, M; Ancowitz, B; Madsen, J; Vanderhoof, J; Shneider, BLBackground & Aims: The apical sodium-dependent bile acid transporter is critical for intestinal reclamation of bile salts, Its expression and activity, along with the ileal lipid-binding protein, were studied before and after intestinal resection in the rat. Methods: The effects of surgical resection and bile acid feeding on the expression of ileal bile acid transport were assessed by a combination of functional (taurocholate uptake into crude brush border membrane vesicles) and molecular assays (Northern and Western blotting), Results: Transport, apical sodium-dependent bile acid transporter and ileal lipid-binding protein messenger RNA and protein expression were restricted to the distal 30 cm of ileum. After resection, transport and expression were limited to the remaining portions of this segment, Limited ileal resection increased protein mass and, therefore, transport in the terminal 5 cm of ileum without a specific increase in transporter gene expression, increased bile acid presentation to the terminal ileum did not induce ileal hyperplasia. Eighty-five percent intestinal resection led to ileal hypertrophy and a specific repression in bile acid transport activity. Conclusions: Native and compensatory bile acid transporter gene expression occur predominantly in the terminal 30 cm of ileum. The specific ileal responses to intestinal resection are dependent on the extent of resection.