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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1987 Jan 1

PMID 3540969

Citations 14

Authors

J D Butler

M E Comly

H S Kruth

M Vanier

J Fink

N Barton

H Weintroub

J M Quirk

T Tokoro

Affiliations

Soon will be listed here.

Abstract

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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