Accumulation of Cholesterol Esters in ex vivo Lymphocytes from Scrapie-susceptible Sheep and in Scrapie-infected Mouse Neuroblastoma Cell Lines
- 1 University of Cagliari, Italy
Abstract
Our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie in sheep, revealed abnormal accumulation of cholesterol esters in brains and in ex vivo skin fibroblasts from genetically scrapie-susceptible, as compared to sheep with resistant genotype. We now report that PBMCs isolated from scrapie-susceptible sheep, as well as mouse neuroblastoma cell lines persistently infected with two different mouse-adapted strains of scrapie, showed similar alterations with up to 3-fold higher cholesterol ester levels than their resistant or uninfected counterparts. Treatments with drugs that interfere with intracellular cholesterol metabolism strongly reduced accumulation of cholesterol esters in scrapie-infected cell lines, whereas had significantly lower, or no effect, in uninfected cell line. These data add support to our hypothesis that accumulation of cholesterol esters may represent a biological marker of susceptibility to prion infection and a potential molecular target for prion inhibitors.
DOI: https://doi.org/10.3844/ajidsp.2007.165.168
Copyright: © 2007 Alessandra Pani, Claudia Norfo, Claudia Abete, Claudia Mulas, Marirosa Putzolu, Sergio Laconi, Christina Doriana Orrù, M. Dolores Cannas, Sarah Vascellari, Paolo La Colla and Sandra Dessì. This is an open access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- scrapie
- prion protein
- cholesterol esters
- inhibitors