ROGLER, G and TRUMBACH, B and KLIMA, B and LACKNER, KJ and SCHMITZ, G (1995) HIGH-DENSITY LIPOPROTEIN-MEDIATED EFFLUX OF NEWLY SYNTHESIZED CHOLESTEROL AND PHOSPHOLIPIDS IS IMPAIRED IN FIBROBLASTS FROM TANGIER PATIENTS WHILE MEMBRANE DESORPTION AND EFFLUX OF LYSOSOMAL CHOLESTEROL ARE NORMAL. NIEREN-UND HOCHDRUCKKRANKHEITEN, 24 (2). pp. 81-83. ISSN 0300-5224,
Full text not available from this repository.Abstract
Mononuclear phagocytes (MNPs) from Tangier patients have been shown previously by our laboratory to have a defect in the interaction with high density lipoproteins (HDL) and abnormalities in the intracellular traffic of lipoproteins and lipids. Similar to Tangier MNPs, fibroblasts show marphologic abnormalities of the Golgi apparatus and abnormal rate of synthesis and catabolism for cellular lipids, indicating that the cellular defect of the disease is expressed in both cell types. Therefore, transport of cellular lipids from their site of synthesis or storage to the cell membrane and release into the medium was studied in cultured skin fibroblasts from Tangier patients. Different from MNPs, fibroblasts do not internalize appreciable amounts of HDL(3), indicating that uptake and retroendocytosis of HDL(3) is not a relevant metabolic pathway in fibroblasts. When HDL(3)-mediated efflux of newly synthesized cholesterol was determined by incorporation of the radioactive pre cursor (C-14)-mevalonolactone, this was reduced by approximately 80% in Tangier fibroblasts. Similarly, HDL(3)-mediated efflux of phosphatidylcholine and sphingomyelin labelled with (H-3)-choline was reduced by approximately 80% and 30%, respectively. On the other hand, efflux of cholesterol taken up by the LDL-receptor pathway was similar in control and Tangier cells. Desorption of cholesterol and phospholipids, incorporated into the cell membrane by diffusion, was also not different between control and Tangier fibroblasts. These data indicate a specific disturbance in the translocation of newly synthesized cholesterol and phospholipids from their site of synthesis to the cell membrane. This may be due either to a defect in the transport of endogenous cholesterol and phospholipids or to a defect in HDL(3)-mediated translocation of endogenous cholesterol and phospholipids.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; TANGIER DISEASE; FIBROBLASTS; HDL(3); CHOLESTEROL EFFLUX |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52775 |
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