title: Understanding the biological activity of amyloid proteins in vitro: from inhibited cellular MTT reduction to altered cellular cholesterol homeostatis.
abstract: 1. MTT is taken into the cell through endocytosis and is reduced and accumulated in a population of acidic vesicles. Reduced MTT formazan is exocytosed to form needle-like formazan crystals at the cell surface. Mitochondria are unlikely to play a significant role in cellular MTT reduction. 2. Amyloid fibrils inhibit cellular MTT reduction indirectly by enhancing MTT formazan exocytosis. All protein fibrils with beta-pleated sheet structure which have been examined enhance MTT formazan exocytosis and induce neurotoxicity. 3. Cellular free cholesterol regulates the exocytosis of the intracellular MTT formazan-transporting vesicles and these vesicles may be involved in cellular cholesterol homeostasis. 4. Amyloid fibrils inhibit cholesterol esterification and alter the distribution of free cholesterol in neurons. 5. Amyloid fibril-induced alterations in cellular cholesterol metabolism and vesicle trafficking may contribute to neurodegeneration in vivo.
authors.affiliation: Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000682:Amyloid / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000502:physiology; D013778:Tetrazolium Salts / Q000378:metabolism*
chemical_list: D000682:Amyloid; D013778:Tetrazolium Salts; D002784:Cholesterol