Caveolin-1 is not required for murine intestinal cholesterol transport

Mark A. Valasek, Jian Weng, Philip W. Shaul, Richard G W Anderson, Joyce J. Repa

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Caveolin-1 (CAV1) is the structural protein of the filamentous coat that decorates the cytoplasmic surface of each caveola. Cell culture studies have implicated CAV1 in playing an important role in intracellular cholesterol trafficking. In addition, it has been reported that CAV1 forms a detergent-resistant protein complex with Annexin-2 in enterocytes that can be disrupted by the cholesterol absorption inhibitor ezetimibe, suggesting a possible role for CAV1 in cholesterol absorption. In this report, we have evaluated cholesterol homeostasis in Cav1 knock-out mice. Deletion of CAV1 does not result in either a compensatory increase of CAV2 or CAV3 in intestine. In addition, Cav1 knock-out mice display normal mRNA and protein levels of Annexin-2 or the putative cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) in proximal intestinal mucosa. Fractional cholesterol absorption and fecal neutral sterol excretion are statistically similar in Cav1 knock-out mice and their wild-type littermates. Moreover, oral administration of ezetimibe is equally effective in decreasing cholesterol absorption in Cav1 null mice and wild-type controls. The mRNA expression levels of genes sensitive to intracellular cholesterol concentration (ATP-binding cassette transporters ABCA1 and ABCG5, hydroxymethylglutaryl-CoA synthase and the LDL receptor) are similarly altered in the proximal intestinal mucosa of Cav1 null and wild-type mice following ezetimibe treatment. These results demonstrate that CAV1 is not required for cholesterol absorption or ezetimibe sensitivity in the mouse.

Original languageEnglish (US)
Pages (from-to)28103-28109
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number30
DOIs
StatePublished - Jul 29 2005

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Caveolin 1
Cholesterol
Knockout Mice
Annexins
Intestinal Mucosa
Hydroxymethylglutaryl-CoA Synthase
Anticholesteremic Agents
Caveolae
Messenger RNA
Proteins
ATP-Binding Cassette Transporters
Enterocytes
LDL Receptors
Capsid Proteins
Sterols
Cell culture
Detergents
Intestines
Oral Administration
Carrier Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Caveolin-1 is not required for murine intestinal cholesterol transport. / Valasek, Mark A.; Weng, Jian; Shaul, Philip W.; Anderson, Richard G W; Repa, Joyce J.

In: Journal of Biological Chemistry, Vol. 280, No. 30, 29.07.2005, p. 28103-28109.

Research output: Contribution to journalArticle

Valasek, Mark A. ; Weng, Jian ; Shaul, Philip W. ; Anderson, Richard G W ; Repa, Joyce J. / Caveolin-1 is not required for murine intestinal cholesterol transport. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 30. pp. 28103-28109.
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