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-Tocopherol Metabolism Is Abnormal in Scavenger Receptor Class B Type I (SR-BI)-Deficient Mice1




Departamentos de
*
Gastroenterología and
**
Nutrición, Diabetes y Metabolismo;
Facultad de Medicina and Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica, Santiago, Chile; and
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 01239
2To whom correspondence should be addressed. E-mail: arigotti{at}med.puc.cl
Despite the physiologic importance of vitamin E, in particular its
-tocopherol (
-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for
-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of
-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma
-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated
-T content of their abnormally large plasma HDL-like particles. This increase in plasma
-T in SR-BI knockout mice was accompanied by a significant decrease (6580%) in the
-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the
-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring
-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of
-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein
-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.
KEY WORDS: lipoproteins LDL receptor vitamin E mice scavenger receptor class B type I
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