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J. Biol. Chem., Vol. 281, Issue 8, 4739-4745, February 24, 2006
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Scavenger Receptor Class B Type I (SR-BI) Is Involved in Vitamin E Transport across the Enterocyte*
1
From the
INSERM U476, 27 boulevard Jean Moulin, 1260 Institut National de la Recherche Agronomique (INRA), Université AixMarseille, and Institut de Physiopathologie Humaine de Marseille (IPMH), Marseille F-13385, France,INSERM U498, 7 boulevard Jeanne d'Arc BP 87900, Dijon F-21079, France, and ¶INSERM U563, Hôpital Purpan, place Baylac, Toulouse F-31024, France
Although cellular uptake of vitamin E was initially described as a passive process, recent studies in the liver and brain have shown that SR-BI (scavenger receptor class B type I) is involved in this phenomenon. As SR-BI is expressed at high levels in the intestine, the present study addressed the involvement of SR-BI in vitamin E trafficking across enterocytes. Apical uptake and efflux of the main dietary forms of vitamin E were examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium. (R,R,R)-
-tocopherol bioavailability was compared between wild-type mice and mice overexpressing SR-BI in the intestine. The effect of vitamin E on enterocyte SR-BI mRNA levels was measured by real-time quantitative reverse transcription-PCR. Concentration-dependent curves for vitamin E uptake were similar for (R,R,R)-
-, (R,R,R)--, and DL--tocopherol. (R,R,R)--tocopherol transport was dependent on incubation temperature, with a 60% reduction in absorption at 4 °C compared with 37 °C (p < 0.05). Vitamin E flux in enterocytes was directed from the apical to the basal side, with a relative 10-fold reduction in the transfer process when measured in the opposite direction (p < 0.05). Co-incubation with cholesterol, -tocopherol, or lutein significantly impaired -tocopherol absorption. Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 80% of vitamin E uptake and up to 30% of apical vitamin E efflux (p < 0.05), and similar results were obtained for (R,R,R)--tocopherol. SR-BI mRNA levels were not significantly modified after a 24-h incubation of Caco-2 cells with vitamin E. Finally, (R,R,R)--tocopherol bioavailability was 2.7-fold higher in mice overexpressing SR-BI than in wild-type mice (p < 0.05). The present data show for the first time that vitamin E intestinal absorption is, at least in part, mediated by SR-BI.
Received for publication, August 16, 2005 , and in revised form, December 23, 2005.
* * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: UMR 476 INSERM/1260 INRA, Faculté de Médecine, 27 Bd. Jean-Moulin, 13385 Marseille Cedex 5, France. Tel.: 33-4-91-29-41-02; Fax: 33-4-91-78-21-01; E-mail: Patrick.Borel{at}medecine.univ-mrs.fr.
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