Intestinal Scavenger Receptors Are Involved in Vitamin K1 Absorption

Abstract

Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone.

Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability

“…However, the fact that scavenger-receptor class B-type I (SR-BI), which is encoded by SCARB1 , facilitates in cell culture and in mice the uptake of several molecules with fairly different chemical structures, e.g., cholesterol [25], vitamin E [26], vitamin K [27] and carotenoids [28], does not fit with this assumption. Consequently, another hypothesis might be that this transporter interacts with mixed micelles rather than with free VA molecules and that micelle components and VA then diffuse to the apical membrane.…”

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“…Griptite 293MSR cells were cultured and transfected with either human ABCB1 in pCMV plasmid or empty pCMV plasmid, as previously described (12,13). Transfection efficiency was verified by Western blotting (14).…”

Recent insights on the role and regulation of retinoic acid signaling during epicardial development

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