Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1771, Issue 9, Pages 1140-1147Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2007.05.011
Keywords
intestinal cholesterol absorption; Niemann-Pick C1 like 1; wt and NPCILI-/- mouse brush border membrane vesicle; inhibitors of cholesterol; absorption; ezetimibe; apolipoprotein A-I
Funding
- NHLBI NIH HHS [HL 22633] Funding Source: Medline
- NIDDK NIH HHS [DK 65793] Funding Source: Medline
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We compared cholesterol uptake into brush border membrane vesicles (BBMV) made from the small intestines of either wild-type or Niemann-Pick C1-like 1 (NPC1L1) knockout mice to elucidate the contribution of NPC1L1 to facilitated uptake; this uptake involves cholesterol transport from lipid donor particles into the BBM of enterocytes. The lack of NPC1L1 in the BBM of the knockout mice had no effect on the rate of cholesterol uptake. It follows that NPC1L1 cannot be the putative high-affinity, ezetimibe-sensitive cholesterol transporter in the brush border membrane (BBM) as has been proposed by others. The following findings substantiate this conclusion: (1) NPC1L1 is not a brush border membrane protein but very likely localized to intracellular membranes; (11) the cholesterol absorption inhibitor ezetimibe and its analogues reduce cholesterol uptake to the same extent in wild-type and NPC1L1 knockout mouse BBMV These findings indicate that the prevailing belief that NPC1L1 facilitates intestinal cholesterol uptake into the BBM and its interaction with ezetimibe is responsible for the inhibition of this process can no longer be sustained. (C) 2007 Elsevier B.V. All rights reserved.
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