title: 25-Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann-Pick disease type C astrocytes.
abstract: 25-hydroxycholesterol (25-OHC), an oxysterol that potently regulates cellular cholesterol metabolism, induced formation of novel fibrillar structures in normal mouse astrocytes as observed by fluorescence microscopy with the cholesterol probe, filipin. These fibrils were identified as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnormal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosomal cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes.
authors.affiliation: Department of Neurology, University of Connecticut Health Center, Farmington 06030.
authors.forename: S C
authors.initials: SC
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Asotra
authors.forename: Y C
authors.initials: YC
authors.lastname: Patel
authors.forename: R C
authors.initials: RC
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000648:ultrastructure; D006888:Hydroxycholesterols / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008818:Mice, Neurologic Mutants; D009542:Niemann-Pick Diseases / Q000188:drug therapy* / Q000473:pathology; D012016:Reference Values
chemical_list: D006888:Hydroxycholesterols; C007997:25-hydroxycholesterol