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© 2002 The American Society for Nutritional Sciences J. Nutr. 132:443-449, 2002


Nutrient Metabolism

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

Pablo Mardones*, Pablo Strobel{dagger}, Soledad Miranda{dagger}, Federico Leighton{dagger}, Verónica Quiñones*, Ludwig Amigo*, Jaime Rozowski**, Monty Krieger{ddagger} and Attilio Rigotti*2

Departamentos de * Gastroenterología and ** Nutrición, Diabetes y Metabolismo; {dagger} Facultad de Medicina and Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica, Santiago, Chile; and {ddagger} 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 {alpha}-tocopherol ({alpha}-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 {alpha}-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 {alpha}-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 {alpha}-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated {alpha}-T content of their abnormally large plasma HDL-like particles. This increase in plasma {alpha}-T in SR-BI knockout mice was accompanied by a significant decrease (65–80%) in the {alpha}-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the {alpha}-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring {alpha}-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 {alpha}-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein {alpha}-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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