A defect in cholesterol esterification in Niemann-Pick disease (type C) patients.
- 1 December 1985
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 82 (23) , 8247-8251
- https://doi.org/10.1073/pnas.82.23.8247
Abstract
The demonstration of a defect of cholesterol esterification in a mutant strain of BALB/c mice with an attendant reduction of sphingomyelinase activity [Pentchev, P. G., Boothe, A. D., Kruth, H.S., Weintroub, H., Stivers, J. & Brady, R. O. (1984) J. Biol. Chem. 259, 5784-5791] prompted us to examine the capacity of cultured human Niemann-Pick fibroblasts to esterify exogenously derived cholesterol. Cholesterol was supplied to cell cultures in the form of native or chemically modified, positively charged low density lipoprotein or as non-lipoprotein cholesterol. Cholesterol esterification was not impaired in cell cultures derived from patients with type A or B Niemann-Pick disease. However, esterification of exogenously administered cholesterol was deficient in 20 type C Niemann-Pick cell lines that were available for testing. Fluorescence histochemical staining of unesterified cholesterol in type C cells suggested that these cells were able to internalize and lysosomally process lipoprotein cholesterol. Acyl-CoA:cholesterol acyltransferase activity did not appear deficient in type C cell extracts. The error in cholesterol esterification may provide an opportunity for probing the molecular lesion in this disorder and may afford a useful and reliable means for establishing diagnosis.This publication has 15 references indexed in Scilit:
- Uptake and metabolism of radioactively labeled sphingomyelin in cultured skin fibroblasts from controls and patients with niemann-pick disease and other lysosomal storage diseasesBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1983
- A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidaseBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1980
- Quantification of low density lipoprotein binding and cholesterol accumulation by single human fibroblasts using fluorescence microscopy.Journal of Lipid Research, 1980
- The Low-Density Lipoprotein Pathway and its Relation to AtherosclerosisAnnual Review of Biochemistry, 1977
- Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts.Proceedings of the National Academy of Sciences, 1976
- A Practical Chromogenic Procedure for the Detection of Homozygotes and Heterozygous Carriers of Niemann-Pick DiseaseNew England Journal of Medicine, 1975
- Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.Journal of Clinical Investigation, 1975
- Staining of cholesterol with the fluorescent antibiotic "filipin".1974
- The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick diseae.Proceedings of the National Academy of Sciences, 1966
- A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUESJournal of Biological Chemistry, 1957