ULTRA-STRUCTURAL STUDIES OF THE ACCUMULATION OF CHOLESTEROLS IN LYSOSOME OF FIBROBLAST CELL LINES DERIVED FROM NIEMANN-PICK TYPE C PATIENTS
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Date
2013-05
Type of Work
Department
Hood College Biology
Program
Biomedical and Environmental Science
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Abstract
Niemann-Pick disease, type C (NPC), is a fatal autosomal recessive lysosomal
storage disorder resulting in fatal neurodegeneration. It is caused by mutations in either of
two genes Npc1 or Npc2 that results in accumulation of unesterified cholesterol and
glycosphingolipids in lysosomes.
Delta-Tocopherol and Methyl-Beta-Cyclodextrin have shown to reduce
cholesterol accumulation in NPC cells. In this thesis, we used room temperature TEM
and high pressure freeze/freeze substitution TEM methods for ultrastructural analysis of
healthy control, NPC, and NPC cells treated with delta-tocopherol and methyl-betacyclodextrin.
HPF method significantly improved ultrastructure of these cells. We
showed vast and enlarged late endosome/lysosome with multi-lamellar, multi-vesicular
and osmiophilic dense bodies as the pathological phenotype of NPC cells. We showed
delta-tocopherol and methyl-beta-cyclodextrin significantly reduced cholesterol
accumulation by reducing the number and size of enlarged late endosome/lysosome
compartments in NPC cells. Our results were based on combined data from fluorescence
microscopy, RT-TEM and HPF-TEM ultrastructural analysis.