title: Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice.
abstract: 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.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Mardones
authors.forename: Pablo
authors.initials: P
authors.lastname: Strobel
authors.forename: Soledad
authors.initials: S
authors.lastname: Miranda
authors.forename: Federico
authors.initials: F
authors.lastname: Leighton
authors.forename: Verónica
authors.initials: V
authors.lastname: Quiñones
authors.forename: Ludwig
authors.initials: L
authors.lastname: Amigo
authors.forename: Jaime
authors.initials: J
authors.lastname: Rozowski
authors.forename: Monty
authors.initials: M
authors.lastname: Krieger
authors.forename: Attilio
authors.initials: A
authors.lastname: Rigotti
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001923:Brain Chemistry; D018955:CD36 Antigens; D005260:Female; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016296:Mutagenesis; D010053:Ovary / Q000737:chemistry; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000172:deficiency; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013737:Testis / Q000737:chemistry; D014162:Transfection; D024502:alpha-Tocopherol / Q000032:analysis / Q000097:blood / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D024502:alpha-Tocopherol