?-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice

Mardones P.; Quiñones V.; Amigo, L; Rigotti, A.; Rozowski J.; Strobel P.; Miranda, S.; Leighton F.; Krieger M.

Keywords: chemistry, proteins, system, density, membrane, transport, reproduction, mouse, endocytosis, animals, culture, lipoproteins, brain, blood, ldl, tocopherol, alpha-tocopherol, cell, liver, testis, cholesterol, alpha, bile, mice, metabolism, antioxidant, experiment, lung, cardiovascular, lipoprotein, male, receptor, mutagenesis, level, ovary, scavenging, tissue, hdl, bioaccumulation, female, excretion, drug, article, ester, bi, vitamin, function, lipid, scavenger, low, transfection, class, controlled, biliary, immunologic, animal, knockout, study, nonhuman, Receptors,, Animalia, Inbred, High, Antigens,, Mice,, C57BL, unclassified, b, CD36, Lipoproteins,

Abstract

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 (65-80%) 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.

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Título según SCOPUS: ?-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice
Título de la Revista: JOURNAL OF NUTRITION
Volumen: 132
Número: 3
Editorial: Elsevier Science Inc.
Fecha de publicación: 2002
Página de inicio: 443
Página final: 449
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0036193774&partnerID=q2rCbXpz
Notas: SCOPUS