Class III P-glycoproteins mediate the formation of lipoprotein X in the mouse
| Autor: | R P Elferink, C. M. G. Frijters, A J Smith, J van Marle, Albert K. Groen, Roelof Ottenhoff |
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| Přispěvatelé: | Other departments, Faculteit der Geneeskunde |
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
ATP Binding Cassette Transporter Subfamily B Hypercholesterolemia Phospholipid Mice Transgenic Biology Mice chemistry.chemical_compound Cholestasis Internal medicine Phosphatidylcholine medicine Animals Humans Lipoprotein-X Cholesterol Vesicle General Medicine medicine.disease Endocrinology chemistry ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) Density gradient ultracentrifugation Bile Ducts Research Article Lipoprotein |
| Zdroj: | Journal of clinical investigation, 102(9), 1749-1757. The American Society for Clinical Investigation The journal of clinical investigation, 102, 1749-1757. The American Society for Clinical Investigation |
| ISSN: | 0021-9738 |
| Popis: | Cholestasis is associated with hypercholesterolemia and ap- pearance of the abnormal lipoprotein X (LpX) in plasma. Using mice with a disrupted Mdr2 gene, we tested the hy- pothesis that LpX originates as a biliary lipid vesicle. Mdr2- deficient mice lack Mdr2 P-glycoprotein, the canalicular translocator for phosphatidylcholine, and secrete virtually no phospholipid and cholesterol in bile. Bile duct ligation of Mdr2 1 / 1 mice induced a dramatic increase in the plasma cholesterol and phospholipid concentration. Agarose elec- trophoresis, density gradient ultracentrifugation, gel perme- ation, and electron microscopy revealed that the majority of phospholipid and cholesterol was present as LpX, a 40—100 nm vesicle with an aqueous lumen. In contrast, the plasma cholesterol and phospholipid concentration in Mdr2 2 / 2 mice decreased upon bile duct ligation, and plasma fractionation revealed a complete absence of LpX. In mice with various expression levels of Mdr2 or MDR3 , the human homolog of Mdr2 , we observed that the plasma level of cholesterol and phospholipid during cholestasis correlated very closely with the expression level of these canalicular P-glycoproteins. These data demonstrate that during cholestasis there is a quantitative shift of lipid secretion from bile to the plasma compartment in the form of LpX. The concentration of this lipoprotein is determined by the activity of the canalicular phospholipid translocator. ( J. Clin. Invest. 1998. 102:1749— |
| Databáze: | OpenAIRE |
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