Niemann-Pick Variant Disorders: Comparison of Errors of Cellular Cholesterol Homeostasis in Group D and Group C Fibroblasts

Fluorescence microscopic examination of filipin-stained cultured skin fibroblasts derived from two brothers with group D Niemann-Pick disease revealed abnormal storage of low density lipoprotein (LDL)-derived cholesterol. LDL stimulation of intracellular cholesteryl ester synthesis was severely comp...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 84; no. 2; pp. 556 - 560
Main Authors Butler, Jean DeBrohun, Comly, Marcella E., Kruth, Howard S., Vanier, Marie, Filling-Katz, Michele, Fink, John, Barton, Norman, Weintroub, Hana, Quirk, Jane M., Tokoro, Toshioharu, Marshall, Darlene C., Brady, Roscoe O., Pentchev, Peter G.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 01.01.1987
National Acad Sciences
Subjects
Adult
Cell culture techniques
Cell lines
Child
Cholesterol - metabolism
Cholesterol esters
Cholesterols
Cultured cells
Disorders
Female
Fibroblasts
Fibroblasts - metabolism
Fluorescent Antibody Technique
Genetic Variation
Heterozygote
Homeostasis
Homozygote
Humans
Kinetics
Lesions
Male
Niemann Pick diseases
Niemann-Pick Diseases - genetics
Niemann-Pick Diseases - metabolism
Skin - metabolism
Ungulates
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Summary:Fluorescence microscopic examination of filipin-stained cultured skin fibroblasts derived from two brothers with group D Niemann-Pick disease revealed abnormal storage of low density lipoprotein (LDL)-derived cholesterol. LDL stimulation of intracellular cholesteryl ester synthesis was severely compromised in the Niemann-Pick D fibroblasts, as it also was in fibroblasts obtained from Niemann-Pick C patients. Cholesteryl ester synthesis was intermediately deficient in cells derived from an obligate group-D heterozygous carrier. Activity of acyl-CoA:cholesterol acyltransferase was within the normal range in cell-free extracts of both LDL-depleted and LDL-supplemented cultures of Niemann-Pick C and D fibroblasts. Incubation of Niemann-Pick D fibroblasts with LDL did not lead to as high a level of intracellular cholesterol accumulation as the excessive storage observed with Niemann-Pick C fibroblasts. These findings suggest that the Niemann-Pick variant disorders may represent a family of specific and possibly individual mutations that disrupt cellular cholesterol homeostasis.
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ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.2.556