Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts.

Abstract

Incubation of mutant Niemann-Pick C fibroblasts with low-density lipoprotein (LDL) resulted in excessive internalization of lipoprotein and extensive cellular over-accumulation of unesterified cholesterol. The uptake of LDL by the mutant cells appeared to occur through the classic LDL receptor pathway and internalized lipoprotein was processed in lysosomes. Lipoprotein uptake into mutant cells was associated with delays in the initiation of established cellular cholesterol homeostatic responses. Subcellular fractionation of mutant Niemann-Pick C fibroblasts accumulating LDL-cholesterol showed excess unesterified sterol to be localized in the light lysosome-light membrane region of a Percoll gradient, and revealed that cholesterol storage was associated with a specific alteration in the normal profiles of lysosomal marker enzymes.

• Authors: P G Pentchev, M E Comly, H S Kruth, T Tokoro, J Butler, J Sokol, M Filling-Katz, J M Quirk, D C Marshall, S Patel
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 1 Issue 1 Pg. 40-5 (Jul 1987) ISSN: 0892-6638 [Print] United States
• PMID: 3609608 (Publication Type: Journal Article)

Chemical References

• Lipoproteins, LDL
• Cholesterol

Topics

• Cells, Cultured
• Cholesterol (metabolism)
• Fibroblasts (metabolism)
• Humans
• Lipoproteins, LDL (metabolism)
• Niemann-Pick Diseases (metabolism)
• Subcellular Fractions (metabolism)